Chemokine analogs for the treatment of human diseases

ABSTRACT

The present invention is concerned with chemokine analogs, including IL-8 analogs, IP-10 analogs, MIP-1α analogs, RANTES analogs, I-309 analogs, MCP-1 analogs, and CCL28 analogs, that are useful for the treatment of a variety of diseases and disorders, and as an adjunct to the treatment of a variety of diseases and disorders. A therapeutically effective amount of the chemokine analog may be administered to a patient in need of such treatment.

CROSS-REFERENCE TO RELATED APPLICATIONS

Not applicable.

STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSOREDRESEARCH AND DEVELOPMENT

Not applicable.

FIELD OF THE INVENTION

This invention relates to the preparation, design, derivation, and useof peptide agonists and antagonists of chemokines. In one aspect, thisinvention relates to the preparation, design, derivation, or use ofchemokine derivatives, agonists or antagonists of seven humanchemokines: IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, and CCL28 (hMEC).

BACKGROUND OF THE INVENTION

Chemokines (chemoattractant cytokines) are a family of homologous serumproteins of between 7 and 16 kDa, which were originally characterized bytheir ability to induce migration of leukocytes. Most chemokines havefour characteristic cysteines (Cys), and depending on the motifdisplayed by the first two cysteines, they have been classified into CXCor alpha, CC or beta, C or gamma, and CX3C or delta chemokine classes.Two disulfide bonds are formed between the first and third cysteine andbetween the second and fourth cysteine. In general, it was thought thatthe disulfide bridges were required, and Clark-Lewis and co-workersreported that, at least for IL-8, the disulfide bridges are critical forchemokine activity (Clark-Lewis et al., J. Biol. Chem. 269:16075-16081,1994). The only exception to having four cysteines is lymphotactin,which has only two cysteine residues. Thus, lymphotactin manages toretain a functional structure with only one disulfide bond.

In addition, the CXC, or alpha, subfamily has been divided into twogroups depending on the presence of the ELR motif (Glu-Leu-Arg)preceding the first cysteine: the ELR-CXC chemokines and the non-ELR-CXCchemokines (see, e.g., Clark-Lewis, supra, and Belperio et al., “CXCChemokines in Angiogenesis,” J. Leukoc. Biol. 68:1-8, 2000).

ELR-CXC chemokines, such as IL-8, are generally strong neutrophilchemoattractants while non-ELR chemokines, such as IP-10, and SDF-1,predominantly recruit lymphocytes. CC chemokines, such as RANTES,MIP-1-alpha, MCP-1, generally function as chemoattractants formonocytes, basophils, eosinophils, and T-cells but not neutrophils. Ingeneral, chemokines are chemotactic agents that recruit leukocytes tothe sites of injuries.

Specific Chemokines

IL-8

Interleukin-8 (IL-8 or CXCL8) was first identified in 1987 as achemokine with the ability to specifically activate neutrophils. Uponexposure to IL-8, neutrophils are activated, and change their shape.Neutrophils are activated by a process that is probably mediated by anincrease in intracellular calcium levels. This activation allowsneutrophils to migrate across the vascular wall. Secretion of IL-8 canoccur from a wide variety of cells, including other leukocytes,fibroblasts, endothelial cells, and epithelial cells in response toischemia and trauma.

IP-10

Interferon-inducible protein-10 (IP-10 or CXCL10) is induced byinterferon-gamma and TNF-alpha, and is produced by keratinocytes,endothelial cells, fibroblasts and monocytes. IP-10 is thought to play arole in recruiting activated T cells to sites of tissue inflammation(Dufour, et al., “IFN-gamma-inducible protein 10 (IP-10;CXCL10)-deficient mice reveal a role for IP-10 in effector T cellgeneration and trafficking,” J Immunol., 168:3195-204, 2002). Inaddition, IP-10 may play a role in hypersensitivity. It may also play arole in the genesis of inflammatory demyelinating neuropathies(Kieseier, et al., “Chemokines and chemokine receptors in inflammatorydemyelinating neuropathies: a central role for IP-10,” Brain 125:823-34,2002).

MIP-1α

Macrophage inflammatory protein-1-alpha (MIP-1α, MIP-1-alpha or CCL3) isa factor produced by macrophages in response to their stimulation bybacterial endotoxins. It activates neutrophils, eosinophils, andbasophils and appears to play a role in inflammation. Additionally, itis especially potent as a basophil agonist, and appears to act through arapid rise in intracellular calcium, and causes the release ofhistamine, sulfido-leukotrienes, and also plays a role in chemotaxis.MIP-1α may also act to inhibit stem cell proliferation.

RANTES

RANTES (Regulated upon Activation, Normal T-cell Expressed, andpresumably Secreted or CCL5) is a chemokine that acts on T-cells,eosinophils and basophils and assists in recruiting leukocytes toinflammatory sites. In particular, it increases the adherence ofmonocytes to endothelial cells, and selectively supports the migrationof certain types of leukocytes. In some cases, RANTES has been shown toactivate basophils and causes the release of histamines. It may also beinvolved in the proliferation and activation of certain types of killercells.

I-309

I-309 refers to the name of a cDNA clone encoding a chemokine (Miller,et al., “A novel polypeptide secreted by activated human T lymphocytes,”J Immunol., 143(9):2907-16, 1989). I-309 is chemotactic for humanmonocytes, and additionally activates them. However, it appears to haveno effect on neutrophils.

MCP-1

Monocyte chemoattractant (or chemotactic) protein-1 (monocytechemotactic protein-1, MCP-1 or CCL2) is another CCL chemokine. It isexpressed by monocytes, endothelial cells, smooth muscle cells, andcertain types of epithelial cells in culture. The expression of MCP1 isinduced in human peripheral blood mononuclear leukocytes byphytohemagglutinin (PHA), lipopolysaccharide, and IL1. MCP-1 functionsas a chemoattractant for monocytes but not neutrophils. There have beenreports that two point mutations are sufficient for MCP-1 to becomechemotactic for neutrophils. MCP-1 activates monocytes and macrophagesin vivo, as well as basophils. Additionally, it can induce theproliferation and activation of certain types of killer cells.

CCL28

CCL28 (hMEC) is a recently described CC chemokine which may play aparticularly important role in homeostasis or inflammatory responses inthe gastrointestinal system (Wang et al., J. Biol. Chem. 275:22313-23,2000).

SDF-1

Stromal cell-derived factor-1 (SDF-1 or CXCL12) is a CXC chemokine thatdemonstrates in vitro activity with respect to lymphocytes and monocytesbut not neutrophils. It is a highly potent in vivo chemoattractant formononuclear cells. SDF-1 has been shown to induce intracellular actinpolymerization in lymphocytes, and to induce a transient elevation ofcytoplasmic calcium in some cells.

Chemokine Receptors

The receptors for chemokines are G-protein coupled seven-transmembranereceptors. Based on the chemokine class they bind, the receptors havebeen named CXCR1, CXCR2, CXCR3, CXCR4, and CXCR5 (all of which bind CXCchemokines); CCR1 through CCR9 (all of which bind CC chemokines); XCR1(which binds the C chemokine, Lptn); and CX3CR1 (which binds the CX3Cchemokine, fractalkine or neurotactin (See Table 1)).

The chemokines and their receptors have received increasing attention inthe last few years. In addition to their role in HIV pathogenesis, it isnow clear that chemokines participate in many pathological conditionssuch as inflammation and diseases or conditions associated withautoinimune responses. They also play a very important role in normalhomeostasis, including lymphoid development and migration, and thegrowth of bone. As a result of their role in various physiologicalprocesses and pathological conditions and diseases, chemokines haveimportant potential therapeutic applications. TABLE 1 Chemokinereceptors Human chemokine ligands CXCR1 IL-8, GCP-2 CXCR2 IL-8, GCP-2,Gro α, Gro β, Gro γ, ENA-78, PBP CXCR3 MIG, IP-10, I-TAC CXCR4SDF-1/PBSF CCR1 MIP-1 α, MIP-1 β, RANTES, HCC-1, 2, 3, and 4 CCR2 MCP-1,MCP-2, MCP-3, MCP-4 CCR3 Eotaxin-1 eotaxin-2, MCP-3 CCR4 TARC, MDC,MIP-1 α, RANTES CCR5 MIP-1 α, MIP-1 β, RANTES CCR6 MIP-3 α/LARC CCR7MIP-3 β/ELC, 6Ckine/LC CCR8 I-309 CCR9 TECK CCR10 CCL27, CCL28(hMEC)

SUMMARY OF THE INVENTION

This invention relates in one aspect to the design, preparation,derivation, and use of peptide agonists and antagonists of chemokinesreferred to herein as chemokine analogs. In preferred embodiments, thisinvention relates to the design, preparation, derivation, or use ofpeptide agonists or antagonists of a chemokine selected from the groupconsisting of IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, and CCL28(hMEC). In other preferred embodiments, the invention relates to thedesign, preparation, derivation, or use of chemokine analogs derivedfrom one or more of the seven chemokines: IL-8, IP-10, MIP-1α, MCP-1,RANTES, I-309, and CCL28. Particularly preferred embodiments are setforth infra in the Detailed Description of the Invention, Examples andClaims.

Another aspect of the invention is directed towards a method fortreating disease, disorder or abnormal condition comprisingadministering to a patient in need of such treatment a therapeuticallyeffective amount of a chemokine analog having a structure selected fromthe group consisting of sequence al (SEQ ID NO:9) to sequence a 154 (SEQID NO:162), inclusive; sequence b1 (SEQ ID NO:163) to sequence b575 (SEQID NO:728), inclusive; sequence c1 (SEQ ID NO:729) to sequence c160 (SEQID NO:881), inclusive; sequence d1 (SEQ ID NO:882) to sequence d90 (SEQID NO:971), inclusive; sequence e1 (SEQ ID NO:972) to sequence e382 (SEQID NO:1350), inclusive; sequence g2 (SEQ ID NO:1351) to sequence g97(SEQ ID NO:1446), inclusive; and sequence h1 (SEQ ID NO:1447) tosequence h184 (SEQ ID NO:1631), inclusive, in a pharmaceuticallyacceptable carrier.

In preferred embodiments, said disease, disorder or abnormal conditionis selected from the group consisting of autoimmune diseases, acutechronic inflammation, cancer, cardiovascular disease, infectiousdisease, and inflammatory disorders including rheumatoid arthritis,chronic inflammatory bowel disease, chronic inflammatory pelvic disease,multiple sclerosis, asthma, osteoarthritis, atherosclerosis, psoriasis,rhinitis, autoimmunity, and organ transplant rejection. In otherpreferred embodiments, the administration of the compound of theinvention serves to increase the hemocrit, assist in mobilizing andrecovering stem cells, stimulate the production of blood cells, assistin vaccine production, or assist in gene therapy.

A further aspect of this invention relates to therapeutic uses ofchemokine analogs to cure, to manage, or to prevent a disease ordisorder selected from the group consisting of autoimmune diseases,acute chronic inflammation, cancer, cardiovascular disease, infectiousdisease, and inflammatory disorders including rheumatoid arthritis,chronic inflammatory bowel disease, chronic inflammatory pelvic disease,multiple sclerosis, asthma, osteoarthritis, atherosclerosis, psoriasis,rhinitis, autoimmunity, and organ transplant rejection. A further aspectof this invention relates to therapeutic uses of chemokine analogs toincrease the hemocrit, assist in mobilizing and recovering stem cells,stimulate the production of blood cells, or assist in vaccineproduction.

Another aspect of the invention is directed towards providingpharmaceutical compositions of chemokine analogs in order to treat amammal by enhancing or inhibiting the action of a chemokine on itsreceptor. An additional aspect of the invention relates to the use ofpharmaceutical compositions of analogs of human IL-8, EP-10, MIP-1α,MCP-1, RANTES, I-309, or CCL28 to treat a human by enhancing orinhibiting the action of IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, orCCL28 on its respective receptor.

A still further aspect of the invention is a method for modulating theactivity of a chemokine receptor by contacting this chemokine receptorwith a compound comprising a structure selected from the groupconsisting sequence a1 (SEQ ID NO:9) to sequence a154 (SEQ ID NO:162),inclusive; sequence b1 (SEQ ID NO:163) to sequence b575 (SEQ ID NO:728),inclusive; sequence c1 (SEQ ID NO:729) to sequence c160 (SEQ ID NO:881),inclusive; sequence d1 (SEQ ID NO:882) to sequence d90 (SEQ ID NO:971),inclusive; sequence e1 (SEQ ID NO:972) to sequence e382 (SEQ IDNO:1350), inclusive; sequence g2 (SEQ ID NO:1351) to sequence g97 (SEQID NO:1446), inclusive; and sequence h1 (SEQ ID NO:1447) to sequenceh184 (SEQ ID NO:1631), inclusive.

Another aspect of the invention consists of using the chemokine analogsof the invention to treat a patient so as to (a) mobilize intracellularcalcium in the patient, (b) mobilize leukocytes or more specifically,neutrophils, or (c) decrease the toxic effects of a cytotoxic agent onwhite blood cells, leukocytes and/or hematopoietic cells.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a concentration-dependent inhibition of ¹²⁵I-IL-8 bindingto CXCR1 and CXCR2 by IL-8, indicating the affinity of IL-8 for theCXCR1 and CXCR2 receptors. FIG. 1 also shows the binding of the IL-8peptide analogs (competing ligands described in Example 1) to CXCR1and/or CXCR2 receptors on THP-1 cells, a human monocytoid cell line.THP-1 cells were preincubated with IL-8 or IL-8 analog for 30 min, thenwere assessed for ¹²⁵I-IL-8 binding following 2 hr of incubation with¹²⁵I-IL-8. 10 nM of ¹²⁵I-IL-8 was added in the presence of IL-8 or theindicated analogs at the concentrations illustrated. The results areexpressed as percentages of the maximal specific binding that wasdetermined without competing ligand.

FIG. 2 shows the induction of [Ca²⁺]_(i) mobilization by I-309 and I-309analogs. Fluo-4,AM loaded human peripheral blood mononuclear cells(5×10⁶/ml) were stimulated with I-309, Compounds 4, 5, 6, and 7 at theconcentrations indicated. The values represent the mean+/−one S.D.

DETAILED DESCRIPTION OF THE INVENTION

The invention relates to the design, preparation, derivation, and use ofchemokine analogs. In one aspect, this invention is directed to thesynthesis or use of chemokine analogs which bind to receptors for any ofseven human chemokines: IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, andCCL28 (hMEC). In another aspect, the invention is directed to thesynthesis, design, derivation, or use of chemokine analogs orderivatives of one or more of the seven human chemokines: IL-8, IP-10,MIP-1α, MCP-1, RANTES, I-309, and CCL28 (hMEC). In a further aspect, theinvention is directed to the synthesis, design, derivation, or use ofagonist or antagonist analogs of one or more of the following sevenhuman chemokines: IL-8, EP-10, MIP-1α, MCP-1, RANTES, I-309, and CCL28,and derivatives thereof. The invention is not limited in its applicationto the details of structures and the arrangements of components setforth in the following description or illustrated in the drawings andthe figures. Further, it should be understood that in any claimed listor claimed Markush group, those schooled in the art will recognize thatthe invention is also thereby described in terms of any individualmember or subgroup of members of the list or Markush group.Additionally, any individual member of the claimed list or the claimedMarkush group can be removed from the list or Markush group withoutaffecting the patentability of the remaining members.

The sequences of the seven aforementioned human chemokines are shownbelow. First are two CXC chemokines: IL-8, and IP-10; second are five CCchemokines: MIP-1α, MCP-1, RANTES, I-309, and CCL28. IL-B:Ala-Val-Ile-Pro-Arg-Ser-Ala- (SEQ ID NO:1) Lys-Glu-Leu-Arg-Cys-Gln-Cys-Ile-Lys-Thr-Tyr-Ser-Lys-Pro- Phe-His-Pro-Lys-Phe-Ile-Lys-Glu-Leu-Arg-Val-Ile-Glu-Ser- Gly-Pro-His-Cys-Ala-Asn-Thr-Glu-Ile-Ile-Val-Lys-Leu-Ser- Asp-Gly-Arg-Glu-Leu-Cys-Leu-Asp-Pro-Lys-Glu-Asn-Trp-Val- Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-Ser IP-10: Val-Pro-Leu-Ser-Arg-Thr-Val- (SEQ IDNO:2) Arg-Cys-Thr-Cys-Ile-Ser-Ile- Ser-Asn-Gln-Pro-Val-Asn-Pro-Pro-Arg-Ser-Leu-Glu-Lys-Leu- Glu-Ile-Ile-Pro-Ala-Ser-Gln-Phe-Cys-Pro-Arg-Val-Glu-Ile- Ile-Ala-Thr-Met-Lys-Lys-Lys-Gly-Glu-Lys-Arg-Cys-Leu-Asn- Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser- Lys-Glu-Met-Ser-Lys-Arg-Ser- Pro MIP-1αSer-Leu-Ala-Ala-Asp-Thr-Pro- (SEQ ID NO:3) Thr-Ala-Cys-Cys-Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln- Asn-Phe-Ile-Ala-Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-Cys-Ser- Lys-Pro-Gly-Val-Ile-Phe-Leu-Thr-Lys-Arg-Ser-Arg-Gln-Val- Cys-Ala-Asp-Pro-Ser-Glu-Glu-Trp-Val-Gln-Lys-Tyr-Val-Ser- Asp-Leu-Glu-Leu-Ser-Ala RANTES:Ser-Pro-Tyr-Ser-Ser-Asp-Thr- (SEQ ID NO:4) Thr-Pro-Cys-Cys-Phe-Ala-Tyr-Ile-Ala-Arg-Pro-Leu-Pro-Arg- Ala-His-Ile-Lys-Glu-Tyr-Phe-Tyr-Thr-Ser-Gly-Lys-Cys-Ser- Asn-Pro-Ala-Val-Val-Phe-Val-Thr-Arg-Lys-Asn-Arg-Gln-Val- Cys-Ala-Asn-Pro-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn- Ser-Leu-Glu-Met-Ser I-309:Lys-Ser-Met-Gln-Val-Pro-Phe- (SEQ ID NO:5) Ser-Arg-Cys-Cys-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu- Arg-Ala-Ile-Leu-Cys-Tyr-Arg-Asn-Thr-Ser-Ser-Ile-Cys-Ser- Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu-Ala- Cys-Ala-Leu-Asp-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys- Met-Leu-Arg-His-Cys-Pro-Ser- Lys-Arg-LysMCP-1: Gln-Pro-Asp-Ala-Ile-Asn-Ala- (SEQ ID NO:7)Pro-Val-Thr-Cys-Cys-Tyr-Asn- Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr- Arg-Arg-Ile-Thr-Ser-Ser-Lys-Cys-Pro-Lys-Glu-Ala-Val-Ile- Phe-Lys-Thr-Ile-Val-Ala-Lys-Glu-Ile-Cys-Ala-Asp-Pro-Lys- Gln-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln- Thr-Gln-Thr-Pro-Lys-Thr CCL28:Ile-Leu-Pro-Ile-Ala-Ser-Ser- (SEQ ID NO:8) Cys-Cys-Thr-Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu- Glu-Arg-Val-Asn-Met-Cys-Arg-Ile-Gln-Arg-Ala-Asp-Gly-Asp- Cys-Asp-Leu-Ala-Ala-Val-Ile-Leu-His-Val-Lys-Arg-Arg-Arg- Ile-Cys-Val-Ser-Pro-His-Asn-His-Thr-Val-Lys-Gln-Trp-Met- Lys-Val-Gln-Ala-Ala-Lys-Lys-Asn-Gly-Lys-Gly-Asn-Val-Cys- His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asn-Arg-Ala- His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr

The N-terminal region of chemokines is involved in the binding andactivating site of its receptor, as well as is the carboxy terminalregion. The beta sheet structure that connects the two termini appearsto play a role in the stabilization of the CXCR and assuring that thetermini are in the proper conformation.

Examples of these analogs are compounds containing structurescorresponding to various regions or portions of the chemokines. Inpreferred embodiments, the chemokine analog comprises an N-terminalregion and a C-terminal region joined together by means of a linker. Inother preferred embodiments, the amino-acid residues of the chemokine orchemokine analog are cyclized, e.g., by etherification of lysine andserine residues or by other means described infra or known in the art.In still other preferred embodiments, the chemokine analog comprises asequence derived from the wild-type chemokine sequence but with one ormore of the cysteines replaced with another amino acid including naturaland non-natural amino acids). Other preferred embodiments includechemokine analogs comprising an N-terminal region, an internal regioncontaining up to three anti-parallel β-sheets, a C-terminal regioncontaining an α-helical structure, a combination of the N- andC-terminal regions linked together directly, a combination of aN-terminal and internal region, or a combination of an internal andC-terminal region, or finally a combination of N-terminal, internal andC-terminal regions. The regions selected from the N-terminal, internaland C-terminal regions may be 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 20, 25, 30, 35, 40, 41, or 45 amino acids in length.

Examples of such analogs also include a cross combination of onechemokine region to a different region from a different chemokine in thesame or different family. These examples include, but are not limitedto, regions of two CXC chemokines: IL-8, IP-10, and five CC chemokines:MIP-1α, MCP-1, RANTES, I-309, and CCL28.

Chemokine analogs of the invention are useful for treating or preventinginflammatory conditions, autoimmune disorders, cancer, graft rejection,bacterial infection, viral infection, vascular conditions (for example,atherosclerosis, restenosis, systemic lupus erythematosis, andischemia-reperfusion), sepsis, tumorigenesis, and angiogenesis; stemcell mobilization as well as vaccine production and blood cell recoveryfollowing chemotherapy. Inflammatory conditions contemplated by thepresent invention include both acute and chronic inflammatory diseases.Chemokine analogs of the inventions may also prove useful in conductinggene therapy; one manner they may assist in the methods of gene therapyis through an arrest of the cell cycle.

Examples of uses of the chemokine analogs in some aspects of theinvention include, but are not limited to, treatment or management ofarthritis, asthma, colitis/illeitis, psoriasis, atherosclerosis and thelike. Examples of uses of the chemokine analogs in some aspects of theinvention to treat or manage autoimmune conditions include, but are notlimited to, rheumatoid arthritis, multiple sclerosis and otherautoimmunological diseases. Examples of uses of the chemokine analogs insome aspects of the invention to treat or manage cancer include, but arenot limited to, treatment or management of human malignancy/cancer cellmetastasis and relapses. Examples of uses of the chemokine analogs insome aspects of the invention to assist in blood cell recovery include,but are not limited to, blood cell elevation afterchemotherapy/radiotherapy and stem cell mobilization fortransplantations. Examples of uses of the chemokine analogs in someaspects of the invention for vaccine production include, but are notlimited to, enhancement in humoral antibody production, increases inantigen presenting T-cells, increases in dendritic cells andimmunological features known as vaccine induction. Chemokines may alsoplay a role in osteoporosis and thus osteoporosis may be treated bychemokine analogs of the invention. Chemokine analogs of the inventionmay also prove useful in treating genetic disease through gene therapy.

As defined by the present invention a chemokine analog acts as anagonist or an antagonist to a native chemokine. The agonistic activityof the chemokine analogs of the present invention includes mimicking ofbiological activity induced by corresponding native chemokines. Theantagonistic activity of the chemokine analogs of the present inventionincludes inhibition of biological activity induced by native chemokines.The instant invention also encompasses a chemokine analog that acts asan agonist or an antagonist to a different native chemokine.

Peptides

In this application, the products of the present invention are referredto by various terms, including “analogs” of the present invention,“chemokine mimetics,” “chemokine analogs,” and “chemokine derivatives.”These terms are used interchangeably and denote equivalent compounds.The term “polypeptides of the present invention,” may also be usedherein to refer to chemokine analogs. Chemokine analogs of the presentinvention comprise a structure which comprises a sequence selected fromthe group set forth as SEQ ID NO:9 through SEQ ID NO:1631, and thus maycomprise additional elements such as R-group substituents and a linkerselected from the possibilities set forth in the instant invention.

As defined by the present invention, biological activity refers to thebiological activity of the native chemokines, as defined and measured bythe scientific reports known to those of skill in the art, andexemplified in the following review articles (Bruce, L. et al.,“Radiolabeled Chemokine binding assays,” Methods in Molecular Biology(2000) vol. 138, pp129-134, Raphaele, B. et al. “Calcium Mobilization,”Methods in Molecular Biology (2000) vol. 138, pp143-148, Paul D. Ponathet aL, “Transwell Chemotaxis,” Methods in Molecular Biology (2000) vol.138, pp113-120 Humana Press. Totowa, N.J.). Aspects of biologicalactivity include, but are not limited to, receptor binding, chemotaxis,calcium mobilization, along with other activities recognized by those ofskill in the art.

The amino acids are identified in the present application by theconventional one-letter and three-letter abbreviations as indicatedbelow, and are preceded by “L-” to indicate their L-form and by “D-” torefer to their D form. These abbreviations are generally accepted in thepeptide art as recommended by the IUPAC-IUB commission in biochemicalnomenclature: Alanine A Ala Leucine L Leu Arginine R Arg Lysine K LysAsparagine N Asn Methionine M Met Aspartic acid D Asp Phenylalanine FPhe Cysteine C Cys Proline P Pro Glutamic acid E Glu Serine S SerGlutamine Q Gln Threonine T Thr Glycine G Gly Tryptophan W Trp HistidineH His Tyrosine Y Tyr Isoleucine I Ile Valine V Val Ornithine O Orn

All of the peptide sequences set out herein are written according to thegenerally accepted convention whereby the N-terminal amino acid is onthe left and the C-terminal amino acid is on the right.

Chemokine mimetics of the invention may include chemokine derivatives orchemokine analogs and their derivatives, such as C-terminalhydroxymethyl derivatives, O-modified derivatives (e.g., C-terminalhydroxymethyl benzyl ether), N-terminally modified derivatives includingsubstituted amides such as alkylamides and hydrazides and compounds inwhich a C-terminal phenylalanine residue is replaced with aphenethylamide analogue (e.g., Ser-Ile-phenethylamide as an analog ofthe tripeptide Ser-Ile-Phe), glycosylated chemokine derivatives,polyethylene glycol modified derivatives, or biotinylated derivatives.Chemokine analogs of the invention include pharmaceutically acceptablesalts of the chemokine analogs.

Modifying Groups

In one aspect of the invention, the chemokine analogs of the invention,(such as peptides derived from IL-8, IP-10, MIP-1α, MCP-1, RANTES,I-309, or CCL28) may be coupled directly or indirectly to at least onemodifying group. In some aspects of the invention, the term “modifyinggroup” is intended to include structures that are directly attached tothe peptidic structure (e.g., by covalent bonding or covalent coupling),as well as those that are indirectly attached to the peptidic structure(e.g., by a stable non-covalent bond association or by covalent couplingthrough a linker to additional amino acid residues). In other aspects ofthe invention the term “modifying group” may also refer to mimetics,analogues or derivatives thereof, which may flank the IL-8, IP-10,MIP-1α, MCP-1, RANTES, I-309, or CCL28 core peptidic structure. Forexample, the modifying group can be coupled to the amino-terminus orcarboxy-terminus of an IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, orCCL28 peptidic structure, or to a peptidic or peptidomimetic regionflanking the core structure. Alternatively, the modifying group can becoupled to a side chain of at least one amino acid residue of an IL-8,IP-10, MIP-1α, MCP-1, RANTES, I-309, or CCL28 peptidic structure, or toa peptidic or peptido-mimetic region flanking the core domain (e.g.,through the epsilon amino group of a lysyl residue(s); through thecarboxyl group of an aspartic acid residue(s) or a glutamic acidresidue(s); through a hydroxy group of a tyrosyl residue(s), a serineresidue(s) or a threonine residue(s); or any other suitable reactivegroup on an amino acid side chain). In other aspects, modifying groupscovalently coupled to the peptidic structure can be attached by meansand using methods well known in the art for linking chemical structures,including, for example, amide, alkylamino, sulfide, carbamate or ureabonds.

In some embodiments, the modifying group may comprise a cyclic,heterocyclic or polycyclic group. The term “cyclic group,” as usedherein, includes cyclic saturated or unsaturated (i.e., aromatic) grouphaving from 3 to 10; from 4 to 8; or 5, 6, or 7 carbon atoms. Exemplarynon-aromatic cyclic groups include cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, and cyclooctyl. The term “heterocyclic group” includesoptionally substituted, saturated or unsaturated, three- toeight-membered cyclic structures in which one or more skeletal atoms isoxygen, nitrogen, sulfur, or combinations thereof. Cyclic groups may beunsubstituted or substituted at one or more ring positions. A cyclicgroup may for example be substituted with halogens, alkyls, cycloalkyls,alkenyls, alkynyls, aryls, arylalkyls, heterocycles, hydroxyls, aminos,nitros, thiols amines, imines, amides, phosphonates, phosphines,carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, sulfonates,selenoethers, ketones, aldehydes, esters, —CF₃, —CN. The cyclic groupmay also be linked to a substituent, such as halogens, alkyls,cycloalkyls, alkenyls, alkynyls, aryls, arylalkyls, heterocycles,hydroxyls, aminos, nitros, thiols amines, imines, amides, phosphonates,phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls,sulfonates, selenoethers, ketones, aldehydes, esters, —CF₃, or —CN, bymeans of a saturated or unsaturated chain of 1, 2, 3, 4, 5, 6, 7, 8, ormore carbon atoms; additionally one or more of the carbon atoms may bereplaced with an oxygen, nitrogen, or sulfur atom. Other means oflinking these groups are also possible.

In one embodiment of the invention, chemokines and chemokine analogs aredesigned by replacing all or part of the beta-sheet domain with alinker. In a different embodiment, all or a portion of theamino-terminal domain aid all or a portion of the carboxy-terminaldomain of a chemokine or chemokine analog are connected with a linker.In another embodiment, the chemokines and chemokine analogs are designedso that there are cyclized by covalent modification between residues ofthe peptide. In still other embodiments, the cysteines of the chemokinesare replaced by other amino acids. In further embodiments, chemokinesand chemokine analogs are modified by attaching modifying groups to theamino terminus.

Definitions

The term “heterocyclic group” includes cyclic saturated, unsaturated andaromatic groups having from 3 to 10; from 4 to 8; or 5, 6, or 7 carbonatoms, wherein the ring structure includes about one or moreheteroatoms. Heterocyclic groups include pyrrolidine, oxolane, thiolane,imidazole, oxazole, piperidine, piperazine, morpholine. The heterocyclicring may be substituted at one or more positions with such substituentsas, for example, halogens, alkyls, cycloalkyls, alkenyls, alkynyls,aryls, arylalkyls, other heterocycles, hydroxyl, amino, nitro, thiol,amines, imines, amides, phosphonates, phosphines, carbonyls, carboxyls,silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes,esters, —CF₃, —CN. Heterocycles may also be bridged or fused to othercyclic groups as described below. A linker may also link theheterocyclic group to such substituents as, for example, halogens,alkyls, cycloalkyls, alkenyls, alkynyls, aryls, arylalkyls,heterocycles, hydroxyls, aminos, nitros, thiols amines, imines, amides,phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers,thioethers, sulfonyls, sulfonates, selenoethers, ketones, aldehydes,esters, —CF₃, —CN.

The term “polycyclic group” as used herein is intended to refer to twoor more saturated, unsaturated or aromatic cyclic rings in which two ormore carbons are common to two adjoining rings, so that the rings are“fused rings.” Rings that are joined through non-adjacent atoms aretermed “bridged” rings. Each of the rings of the polycyclic group may besubstituted with such substituents as described above, as for example,halogens, alkyls, cycloalkyls, alkenyls, alkynyls, hydroxyl, amino,nitro, thiol, amines, imines, amides, phosphonates, phosphines,carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls,selenoethers, ketones, aldehydes, esters, —CF₃, or —CN.

The term “alkyl” refers to a saturated aliphatic groups, includingstraight chain alkyl groups, branched-chain alkyl groups, cycloalkyl(alicyclic) groups, alkyl substituted cycloalkyl groups, and cycloalkylsubstituted alkyl groups. In some embodiments, a straight chain orbranched chain alkyl has 20 or fewer carbon atoms in its backbone(C₁-C₂₀ for straight chain, C₃-C₂₀ for branched chain), or 10 or fewercarbon atoms. In some embodiments, cycloalkyls may have from 4-10 carbonatoms in their ring structure, such as rings made from 5, 6 or 7. Unlessthe number of carbons is otherwise specified, “lower alkyl” as usedherein means an alkyl group, as defined above, having from one to tencarbon atoms in its backbone structure. Likewise, “lower alkenyl” and“lower alkynyl” have chain lengths of ten or less carbons.

The term “alkyl” (or “lower alkyl”) as used throughout the specificationand claims is intended to include both “unsubstituted alkyls” and“substituted alkyls,” the latter of which refers to alkyl moietieshaving substituents replacing a hydrogen on one or more carbons of thehydrocarbon backbone. Such substituents can include, for example,halogen, hydroxyl, carbonyl (such as carboxyl, ketones (includingalkylcarbonyl and arylcarbonyl groups)), and esters (includingalkyloxycarbonyl and aryloxycarbonyl groups), thiocarbonyl, acyloxy,alkoxyl, phosphoryl, phosphonate, phosphinate, amino, acylamino, amido,amidine, imino, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate,sulfonate, sulfamoyl, sulfonamido, heterocyclyl, aralkyl, or an aromaticor heteroaromatic moiety. The moieties substituted on the hydrocarbonchain can themselves be substituted, if appropriate. For instance, thesubstituents of a substituted alkyl may include substituted andunsubstituted forms of aminos, azidos, iminos, amidos, phosphoryls(including phosphonates and phosphinates), sulfonyls (includingsulfates, sulfonamidos, sulfamoyls and sulfonates), or silyl groups, aswell as ethers, alkylthios, carbonyls (including ketones, aldehydes,carboxylates, and esters), —CF₃, —CN and the like. Exemplary substitutedalkyls are described below. Cycloalkyls can be further substituted withalkyls, alkenyls, alkoxys, alkylthios, aminoalkyls, carbonyl-substitutedalkyls, —CF3, —CN, and the like.

The terms “alkenyl” and “alkynyl” refer to unsaturated aliphatic groupsanalogous in length and possible substitution to the alkyls describedabove, but that contain at least one double or triple bond respectively.

The term “aralkyl,” as used herein, refers to an alkyl or alkylenylgroup substituted with at least one aryl group. Exemplary aralkylsinclude benzyl (i.e., phenylmethyl), 2-naphthylethyl,2-(2-pyridyl)propyl, 5-dibenzosuberyl, and the like.

The term “alkylcarbonyl,” as used herein, refers to —C(O)-alkyl.Similarly, the term “arylcarbonyl” refers to —C(O)-aryl. The term“alkyloxycarbonyl,” as used herein, refers to the group —C(O)—O-alkyl,and the term “aryloxycarbonyl” refers to —C(O)—O-aryl. The term“acyloxy” refers to —O—C(O)—R₇, in which R₇ is alkyl, alkenyl, alkynyl,aryl, aralkyl or heterocyclyl.

The term “amino,” as used herein, refers to —N(R_(α))(R_(β)), in whichR_(α) and R_(β) are each independently hydrogen, alkyl, alkyenyl,alkynyl, aralkyl, aryl, or in which R_(α) and R_(β) together with thenitrogen atom to which they are attached form a ring having 4-8 atoms.Thus, the term “amino,” as used herein, includes unsubstituted,monosubstituted (e.g., monoalkylamino or monoarylamino), anddisubstituted (e.g., dialkylamino or alkylarylamino) amino groups. Theterm “amido” refers to —C(O)—N(R_(α))(R_(β)), in which R_(α) and R_(β)are as defined above. The term “acylamino” refers to —N(R′_(α))C(O)—R₇,in which R₇ is as defined above and R_(α) is alkyl.

As used herein, the term “nitro” means —NO₂; the term “halogen”designates —F, —Cl, —Br or —I; the term “sulfhydryl” means —SH; and theterm “hydroxyl” means —OH.

The term “aryl” as used herein includes 5-, 6- and 7-membered aromaticgroups that may include from zero to four heteroatoms in the ring, forexample, phenyl, pyrrolyl, furyl, thiophenyl, imidazolyl, oxazole,thiazolyl, triazolyl, pyrazolyl, pyridyl, pyrazinyl, pyridazinyl andpyrimidinyl, and the like. Those aryl groups having heteroatoms in thering structure may also be referred to as “aryl heterocycles” or“heteroaromatics.” The aromatic ring can be substituted at one or morering positions with such substituents as described above, as forexample, halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl,hydroxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate,phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl,sulfonamido, ketone, aldehyde, ester, a heterocyclyl, an aromatic orheteroaromatic moiety, —CF₃, —CN, or the like. Aryl groups can also bepart of a polycyclic group. For example, aryl groups include fusedaromatic moieties such as naphthyl, anthracenyl, quinolyl, indolyl, andthe like.

Modifying groups may also include groups comprising biochemical labelsor structures, such as biotin, fluorescent-label-containing groups,light scattering or plasmon resonant particle, adiethylene-triaminepentaacetyl group, a (O)-menthoxyacetyl group, aN-acetylneuraminyl group, a cholyl structure or an iminobiotinyl group.A chemokine analog or chemokine mimetic compound may be modified at itscarboxy terminus with a cholyl group according to methods known in theart. Cholyl derivatives and analogs may also be used as modifyinggroups. For example, a preferred cholyl derivative is Aic(3-(O-aminoethyl-iso)-cholyl), which has a free amino group that can beused to further modify the chemokine mimetic compound. A modifying groupmay be a “biotinyl structure,” which includes biotinyl groups andanalogues and derivatives thereof (such as a 2-iminobiotinyl group). Inanother embodiment, the modifying group may comprise a fluorescent-labelgroup, e.g., a fluorescein-containing group, such as a group derivedfrom reacting an IL-8, IP-10, MIP-1α, MCP-1, RANTES, I-309, and CCL28derived peptidic structure with 5-(and 6-)-carboxyfluorescein,succinimidyl ester or fluorescein isothiocyanate. The chemokine analogsmay also be modified by attaching other fluorescent labels includingrhodamine, dichlorotriazinylamine fluorescein, dansyl chloride orphycoerythrin and energy transfer fluorescent dyes or fluorescention-indicators. In various other embodiments, the modifying group(s) maycomprise an N-acetylneurarninyl group, a trans4-cotininecarboxyl group,a 2-imino-1-imidazolidineacetyl group, an (S)-(−)-indoline-2-carboxylgroup, a (−)-menthoxyacetyl group, a 2-norbornaneacetyl group, aγ-oxo-5-acenaphthenebutyryl, a (−)-2-oxo-4-thiazolidinecarboxyl group, atetrahydro-3-furoyl group, a 2-iminobiotinyl group, adiethylenetriaminepentaacetyl group, a 4-morpholinecarbonyl group, a2-thiopheneacetyl group or a 2-thiophenesulfonyl group. In otherembodiments, light scattering groups, magnetic groups, nanogold, otherproteins, a solid matrix, radiolabels, or carbohydrates may be attached.

In still other aspects, the modifying group. may be an oligomer, forexample, polyethylene glycol, an oligonucleotide, a polypeptide (whichmay or may not be derived from a chemokine) or one moiety of a bindingpair.

Functional Enhancement

A chemokine analog compound of the invention may be further modified toalter the specific properties of the compound while retaining thedesired functionality of the compound. For example, in one embodiment,the compound may be modified to alter a pharmacokinetic property of thecompound, such as in vivo stability, solubility, bioavailability orhalf-life. The compound may be modified to label the compound with adetectable substance. The compound may be modified to couple thecompound to an additional therapeutic moiety. To further chemicallymodify the compound, such as to alter its pharmacokinetic properties,reactive groups can be derivatized. For example, when the modifyinggroup is attached to the amino-terminal end of the IL-8, IP-10, MIP-1α,MCP-1, RANTES, I-309, and CCL28 core domain, the carboxy-terminal end ofthe compound may be further modified. Potential C-terminal modificationsinclude those that reduce the ability of the compound to act as asubstrate for carboxypeptidases. Examples of C-terminal modifiersinclude an amide group, an ethylamide group and various non-naturalamino acids, such as D-amino acids, β-alanine, C-terminaldecarboxylation, and a C-terminal alcohol. Alternatively, when themodifying group is attached to the carboxy-terminal end of theaggregation core domain, the amino-terminal end of the compound may befurther modified, for example, to reduce the ability of the compound toact as a substrate for aminopeptidases.

Chemokines and chemokine analogs of the invention may be modified by theaddition of polyethylene glycol (PEG). PEG modification may lead toimproved circulation time, improved solubility, improved resistance toproteolysis, reduced antigenicity and immunogenicity, improvedbioavailability, reduced toxicity, improved stability, and easierformulation (For a review see, Francis et al., International Journal ofHematology 68:1-18, 1998). PEGylation may also result in a substantialreduction in bioactivity.

The chemokine analogs of the invention may also be coupled to aradioisotope such as yttrium-90 or iodine-131 for therapeutic purposes(see, e.g., DeNardo et al., “Choosing an optimal radioinmmunotherapydose for clinical response,” Cancer 94(4 Suppl):1275-86, 2002; Kaltsaset al., “The value of radiolabelled MIBG and octreotide in the diagnosisand management of neuroendocrine tumours,” Ann Oncol 12 Suppl 2:S47-50,2001).

Detection Enhancement

A chemokine mimetic compound can be further modified to label thecompound by reacting the compound with a detectable substance. In someaspects of the invention, suitable detectable substances include variousenzymes, prosthetic groups, fluorescent materials, luminescentmaterials, light scattering or ptasmon resonant materials, andradioactive materials. Examples of suitable enzymes include horseradishperoxidase, alkaline phosphatase, beta-galactosidase, oracetylcholinesterase. Examples of suitable prosthetic groups which aremembers of a binding pair and are capable of forming complexes includestreptavidin/biotin, avidinibiotin and an antigen/antibody complex(e.g., rabbit IgG and anti-rabbit IgG). Examples of suitable fluorescentmaterials include umbelliferone, fluorescein, fluoresceinisothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansylchloride or phycoerythrin and energy transfer fluorescent dyes. Anexample of a luminescent material includes luminol. Examples of lightscattering or plasmon resonant materials include gold or silverparticles and quantum dots. Examples of suitable radioactive materialinclude ¹⁴C, ¹²³I, ₁₂₄I, ₁₂₅I, ₁₃₁I, Tc99m, ₃₅S or ³H. A chemokinemimetic compound may be radioactively labeled with ¹⁴C, either byincorporation of ¹⁴C into the modifying group or one or more amino acidstructures in the chemokine mimetic compound. Labeled chemokine mimeticcompounds may be used to assess the in vivo phannacokinetics of thecompounds, as well as to detect disease progression or propensity of asubject to develop a disease, for example for diagnostic purposes.Tissue distribution chemokine receptors can be detected using a labeledchemokine mimetic compound either in vivo or in an in vitro samplederived from a subject. For use as an in vivo diagnostic agent, achemokine mimetic compound of the invention may be labeled withradioactive technetium or iodine. A modifying group can be chosen thatprovides a site at which a chelation group for the label can beintroduced, such as the Aic derivative of cholic acid, which has a freeamino group. For example, a tyrosine residue within the IL-8, IP-10,MIP-1α, MCP-1, RANTES, I-309, and CCL28 sequence may be substituted withradioactive iodotyrosyl. Any of the various isotopes of radioactiveiodine may be incorporated to create a diagnostic or therapeutic agent.¹²³I (half-life=13.2 hours) may be used for whole body scintigraphy,¹²⁴I (half life=4 days) may be used for positron emission tomography(PET), ¹²⁵I (half life=60 days) may be used for metabolic turnoverstudies and ¹³¹I (half life=8 days) may be used for whole body countingand delayed low resolution imaging studies.

Prodrug

In an alternative chemical modification, a chemokine analog compound ofthe invention may be prepared in a “prodrug” form, wherein the compounditself does not act as a chemokine analog agonist, but rather is capableof being transformed, upon metabolism in vivo, into a chemokine analogagonist or antagonist compound as defined herein. For example, in thistype of compound, the modifying group can be present in a prodrug formthat is capable of being converted upon metabolism into the form of anactive chemokine analog agonist. Such a prodrug form of a modifyinggroup is referred to herein as a “secondary modifying group.” A varietyof strategies are known in the art for preparing peptide prodrugs thatlimit metabolism in order to optimize delivery of the active form of thepeptide-based drug.

Synthesis

Chemokine analog compounds of the invention may be prepared by standardtechniques known in the art. A peptide or polypeptide component of achemokine analog may comprise, at least in part, a peptide synthesizedusing standard techniques (such as those described by Clark-Lewis, I.,Dewald, B., Loetscher, M., Moser, B., and Baggiolini, M., (1994) J.Biol. Chem., 269, 16075-16081). Automated peptide synthesizers arecommercially available (e.g., Advanced ChemTech Model 396;Milligen/Biosearch 9600, Appliedbiosystems/Pioneer). Peptides andpolypeptides may be assayed for chemokine receptor agonist or antagonistactivity in accordance with standard methods. Peptides and polypeptidesmay be purified by HPLC and analyzed by mass spectrometry. Peptides andpolypeptides may be dimerized. In one embodiment, peptides andpolypeptides are dimerized via a disulfide bridge formed by gentleoxidation of the cysteines using 10% DMSO in water. Following HPLCpurification, dimer formation may be verified, by mass spectrometry. Oneor more modifying groups may be attached to a MCP-1, RANTES, IL-8,IP-10, MIP-1α, I-309, or CCL28-derived peptidic component by standardmethods, for example, using methods for reaction through an amino group(e.g., the alpha-amino group at the amino-terminus of a peptide), acarboxyl group (e.g., at the carboxy terminus of a peptide), a hydroxylgroup (e.g., on a tyrosine, serine or threonine residue) or othersuitable reactive group on an amino acid side chain.

In alternative embodiments, analogs derived from the C-terminal andN-terminal joined by a linker could be cyclized in their C-terminalmoiety using side-chain to side-chain; side-chain to scaffold or,scaffold to scaffold cyclization. In some embodiments, lactamization,etherification, or RCM (Ring Closing Methatesis) are used to carry outthis reaction.

For instance, chemokine analogs may be cyclized using a lactam formationprocedure by joining the γ-carboxy side chain or the α-carboxy moiety ofglutamate (Glu) residue to the ε-amino side chain of lysine (Lys)residue, as indicated in the following sequences by underlining oflinked residues. Lactams may for example be formed between glutamic acidand lysine (Lys) in the C-terminal portion of the polypeptide (whichdoes not correspond necessarily with the numbering of that residue inthe native sequence). In further alternatives, a lysine (Lys) may besubstituted by ornithine (Orn) or any other (Lor D) natural or (L or D)non-natural amino acid having an amino group on its side chain.Similarly, glutamate (Glu) may for example be substituted with aspartate(Asp), denoted by nomenclature such as (Glu->Asp) indicating asubstitution in a given position in the peptide wherein aspartatereplaces glutamate.

The chemokine analogs of the invention include chemokine polypeptidesequences wherein one or more of the amino acids have been replaced by aconservative amino acid substitution. The term “conservative amino acidsubstitution” refers to a polypeptide chain in which one of the aminoacid residues is replaced with an amino acid residue having a side chainwith similar properties. Families of amino acid residues having sidechains with similar properties are well known in the art. These familiesinclude amino acids with acidic side chains (e.g., aspartic acid,glutamic acid), basic side chains (e.g., lysine, arginine, histidine),uncharged polar side chains (e.g., glycine, asparagine, glutamine,serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g.,alanine, valine, leucine, isoleucine, proline, phenylalanine,methionine, tryptophan), beta-branched side chains (e.g., threonine,valine, isoleucine) and aromatic side chains (e.g., tyrosine,phenylalanine, tryptophan, histidine). Thus, an amino acid residue in achemokine is replaced with another amino acid residue from the same sidechain family.

Recombinant Synthesis

Chemokines, chemokine fragments, or chemokine analogs may also besynthesized, in whole or in part, by recombinant methods usingexpression vectors encoding all or part of a chemokine.

Vectors, or preferably expression vectors, may contain a gene encoding apolypeptide of the invention, a functional derivative thereof, oranother useful polypeptide. These vectors may be employed to express theencoded polypeptide in either prokaryotic or eukaryotic cells.

The term “vector” in this application refers to a DNA molecule intowhich another DNA of interest can be inserted by incorporation into theDNA of the vector. One skilled in the art is familiar with the term.Examples of classes of vectors can be plasmids, cosmids, viruses, andbacteriophage. Typically, vectors are designed to accept a wide varietyof inserted DNA molecules and then used to transfer or transmit the DNAof interest into a host cell (e.g., bacterium, yeast, higher eukaryoticcell). A vector may be chosen based on the size of the DNA molecule tobe inserted, as well as based on the intended use. For transcriptioninto RNA or transcription followed by translation to produce an encodedpolypeptide, an expression vector would be chosen. For the preservationor identification of a specific DNA sequence (e.g., one DNA sequence ina cDNA library) or for producing a large number of copies of thespecific DNA sequence, a cloning vector would be chosen. If the vectoris a virus or bacteriophage, the term vector may include theviral/bacteriophage coat.

Following entry into a cell, all or part of the vector DNA, includingthe insert DNA, may be incorporated into the host cell chromosome, orthe vector may be maintained extrachromosomally. Those vectors that aremaintained extrachromosomally are frequently capable of autonomousreplication in a host cell into which they are introduced (e.g., manyplasmids having a bacterial origin of replication). Other vectors areintegrated into the genome of a host cell upon introduction into thehost cell, and thereby are replicated along with the host genome.

The term “expression vector” refers to a DNA construct which allows oneto place a gene encoding a gene product of interest, usually a protein,into a specific location in a vector from which the selected geneproduct can be expressed by the machinery of the host cell, oralternately, by in vitro expression system. This type of vector isfrequently a plasmid, but other forms of expression vectors, such asbacteriophage vectors and viral vectors (e.g., adenoviruses, replicationdefective retroviruses, and adeno-associated viruses), may be employed.The selection of expression vectors, control sequences, transformationmethods, and the like, are dependent on the type of host cell used toexpress the gene.

Prokaryotic Hosts

Prokaryotic hosts are, in generally, very efficient and convenient forthe production of recombinant polypeptides and are, therefore, one typeof preferred expression system. Prokaryotes most frequently arerepresented by various strains of E. coli, but other microbial strainsmay be used, including other bacterial strains. Recognized prokaryotichosts include bacteria such as E. coli, Bacillus, Streptomyces,Pseudomonas, Salmonella, Serratia, and the like. However, under suchconditions, recombinantly-produced polypeptides will not beglycosylated.

In prokaryotic systems, vectors that contain replication sites andcontrol sequences derived from a species compatible with the host may beused. Preferred prokaryotic vectors include plasmids such as thosecapable of replication in E. coli (such as, for example, pBR322, ColEl,pSC101, pACYC184, pVX, pUC118, pUC119 and the like). Suitable phage orbacteriophage vectors may include λgt10, λgt11, vectors derived fromfilamentous bacteriophage such as m13, and the like. SuitableStreptomyces plasmids include p1J101, and streptomyces bacteriophagessuch as fC31. Bacillus plasmids include pC194, pC221, pT127, and thelike. Suitable Pseudomonas plasmids have been reviewed by Izaki. (Jpn.J. Bacteriol. 33:729-742, 1978) and John et al. (Rev. Infect. Dis.8:693-704, 1986).

To express a protease of the invention (or a functional derivativethereof) in a prokaryotic cell, it is necessary to operably link thesequence encoding the protease of the invention to a functionalprokaryotic promoter. Such promoters are either constitutive orinducible promoters, but commonly inducible promoters are used. Examplesof constitutive promoters include the int promoter of bacteriophage λ,the bla promoter of the β-lactamase gene sequence of pBR322, and the catpromoter of the chloramphenicol acetyl transferase gene sequence-ofpPR325, and the like. Examples of inducible prokaryotic promotersinclude the major right and left promoters of bacteriophage λ (PL andPR), the trp, recA, lacZ, lacI, and gal promoters of E. coli, theα-amylase and the V-28-specific promoters of B. subtilis, the promotersof the bacteriophages of Bacillus, and Streptomyces promoters.Prokaryotic promoters are reviewed by Glick (Ind. Microbiot: 1:277-282,1987), Cenatiempo (Biochimie 68:505-516, 1986), and Gottesman (Ann. Rev.Genet. 18:415-442, 1984). Additionally, proper expression in aprokaryotic cell also requires the presence of a ribosome-binding siteupstream of the encoding sequence. Such ribosome-binding sites aredisclosed, for example, by Gold et al. (Ann. Rev. Microbiol. 35:365-404,1981).

Fusion Protein

Proteins may be expressed as fusion proteins. Genes for proteinsexpressed as fusion proteins ligated into expression vectors that add anumber of amino acids to a protein encoded and expressed, usually to theamino terminus of the recombinant protein. Such a strategy of producingfusion proteins is usually adopted for three purposes: (1) to assist inthe purification by acting as a ligand in affinity purification, (2) toincrease the solubility of the product, and (3) to increase theexpression of the product. Often, expression vectors for use in fusionprotein production, a proteolytic cleavage site is included at thejunction of the fusion region and the protein of interest to enablepurification of the recombinant protein away from the fusion regionfollowing affinity purification of the fusion protein. Such enzymes, andtheir cognate recognition sequences, include Factor Xa, thrombin andenterokinase, and may also include trypsin or chymotrypsin. Typicalfusion expression vectors include pGEX (Pharmacia Biotech Inc; Smith, D.B. and Johnson, K. S. (1988) Gene 67:31-40), pMAL (New England Biolabs,Beverly, Mass.) and pRIT5 (Pharmacia, Piscataway, N.J.) which fuseglutathione S-transferase (GST), maltose E binding protein, or proteinA, respectively, to the target recombinant protein.

Improving Yield

Maximizing recombinant protein expression in E. coli can be assisted byexpressing the protein or fusion protein in a host bacteria with animpaired proteolytic system so as to reduce the post-synthesisdegradation of the recombinant protein (Gottesman, S., Gene ExpressionTechnology: Methods in Enzymology 185, Academic Press, San Diego, Calif.(1990) 119-128). Another strategy is to alter the mix of codons used inthe coding sequence to reflect the usage of the individual codons foreach amino acid in the host (e.g., E. coli (Wada et al., (1992) NucleicAcids Res. 20:2111-2118)). Such alteration of nucleic acid sequences ofthe invention can be carried out by standard DNA synthesis techniquesand may prove useful for a variety of prokaryotic and eukaryoticexpression systems.

Eukaryotic Hosts

Suitable hosts may include eukaryotic cells. Preferred eukaryotic hostsinclude, for example, yeast, fungi, insect cells, and mammalian cellsboth in vivo and in tissue culture. Useful mammalian cell hosts includeHeLa cells, cells of fibroblast origin such as VERO or CHO-K1, and cellsof lymphoid origin and their derivatives. Preferred mammalian host cellsinclude SP2/0 and J558L, as well as neuroblastoma cell lines such as IMR332, which may provide better capacities for correct post-translationalprocessing. In general, eukaryotic organisms such as yeast providesubstantial advantages in that they can also carry outpost-translational modifications.

A large number of yeast expression systems may be potentially utilizedwhich incorporate promoter and termination elements from the activelyexpressed sequences coding for glycolytic enzymes. These expressionsystems produce in large quantities of proteins when yeast are grown inmediums rich in glucose. Known glycolytic gene sequences can alsoprovide very efficient transcriptional control signals. A number ofrecombinant DNA strategies exist utilizing strong promoter sequences andhigh copy number plasmids which can be utilized for production of thedesired proteins in yeast. Examples of vectors suitable for expressionin S. cerivisae include pYepSec1 (Baldari, et al., (1987) Embo J.6:229-234), pMFa (Kurjan and Herskowitz, (1982) Cell 30:933-943), pJRY88(Schultz et al., (1987) Gene 54:113-123), pYES2 (InVitrogen Corporation,San Diego, Calif.), and picZ (InVitrogen Corp, San Diego, Calif.).

In another embodiment, the protein of interest may be expressed ininsect cells for example the Drosophila larvae. Using insect cells ashosts, the Drosophila alcohol dehydrogenase promoter may be used (Rubin,Science 240:1453-1459, 1988). Additionally, baculovirus vectors can beengineered to express large amounts of the protein of interest incultured insect cells (e.g., Sf 9 cells)(Jasny, Science 238:1653, 1987;Miller et al., in: Genetic Engineering, Vol. 8, Plenum, Setlow et al.,eds., pp. 277-297, 1986). Vectors which may be used include the pAcseries (Smith et al. (1983) Mol. Cell Biol. 3:2156-2165) and the pVLseries (Lucklow and Summers (1989) Virology 170:31-39).

Plant cells may also be utilized as hosts, and control sequencescompatible with plant cells are available, such as the cauliflowermosaic virus 35S and 19S promoters, and nopaline synthase promoter andpolyadenylation signal sequences. Furthermore, the protein of interestmay be expressed in plants which have incorporated the expression vectorinto their germ line.

In yet another embodiment, a nucleic acid of the invention may beexpressed in mammalian cells using a mammalian expression vector.Possibilities and techniques for expression in mammalian cells hasrecently been summarized (Colosimo, et al., “Transfer and expression offoreign genes in mammalian cells,” Biotechniques 29(2):314-8, 320-2, 324passim, 2000; which is hereby incorporated by reference in its entiretyincluding any drawings, tables, and figures.). Examples of mammalianexpression vectors include pCDM8 (Seed, B. (1987) Nature 329:840) andpMT2PC (Kaufinan et al. (1987) EMBO J. 6:187-195). For use in mammaliancells, the regulatory sequences of the expression vector are oftenderived from viral regulatory elements. For example, commonly usedpromoters are derived from Simian Virus 40 (SV40), polyoma, Adenovirus2, and cytomegalovirus (CMV) viruses. Preferred eukaryotic promotersinclude, for example, the promoter of the mouse metallothionein I genesequence (Hamer et al., J. Mol. Appl. Gen. 1:273-288, 1982); the TKpromoter of Herpes virus (McKnight, Cell 31:355-365, 1982); the SV40early promoter (Benoist et al., Nature (London) 290:304-31, 1981); andthe yeast gal4 gene sequence promoter (Johnston et al., Proc. Natl.Acad. Sci. (USA) 79:6971-6975, 1982; Silver et al., Proc. Natl. Acad.Sci. (USA) 81:5951-5955, 1984). Alternatively, promoters from mammalianexpression products, such as actin, collagen, myosin, and the like, maybe employed. Regulatory elements may also be derived from adenovirus,bovine papilloma virus, cytomegalovirus, simian virus, or the like.

Transcriptional initiation regulatory signals may be selected whichallow for repression or activation, so that expression of the genesequences can be modulated. Of interest are regulatory signals which aretemperature-sensitive so that by varying the temperature, expression canbe repressed or initiated, or are subject to chemical (such asmetabolite) regulation. Expression of proteins of interest in eukaryotichosts requires the use of eukaryotic regulatory regions. Such regionswill, in general, include a promoter region sufficient to direct theinitiation of RNA synthesis.

The recombinant mammalian expression vector may also be designed to becapable of directing expression of the nucleic acid preferentially in aparticular cell type (i.e., tissue-specific regulatory elements are usedto control the expression). Such tissue-specific promoters include theliver-specific albumin promoter (Pinkert et al. (1987) Genes Dev.1:268-277); lymphoid-specific promoters (e.g., Calame and Eaton (1988)Adv. Immunol. 43:235-275), and in particular promoters ofimmunoglobulins and T cell receptors (Winoto and Baltimore (1989) EMBOJ. 8:729-733, Banerji et al. (1983) Cell 33:729-740; Queen and Baltimore(1983) Cell 33:741-748); mammary gland-specific promoters (e.g., milkwhey promoter; U.S. Pat. No. 4,873,316 and European ApplicationPublication No. 264,166); and pancreas-specific promoters (Edlund et al.(1985) Science 230:912-916). Developmentally-regulated promoters mayalso be utilized, for example, the α-fetoprotein promoter (Campes andTilghman (1989) Genes Dev. 3:537-546), and the murine hox promoters(Kessel and Gruss (1990) Science 249:374-379).

Preferred eukaryotic plasmids include, for example, SV40, BPV, pMAM-neo,pKRC, vaccinia, 2-micron circle, and the like, or their derivatives.Such plasmids are well known in the art (Botstein et al., Miami Wntr.Symp. 19:265-274, 1982; Broach, In: “The Molecular Biology of the YeastSaccharomyces: Life Cycle and Inheritance,” Cold Spring HarborLaboratory, Cold Spring Harbor, N.Y., p. 445-470, 1981; Broach, Cell28:203-204, 1982; Bollon et al., J. Clin. Hematol. Oncol. 10:39-48,1980; Maniatis, In: Cell Biology: A Comprehensive Treatise, Vol. 3, GeneSequence Expression, Academic Press, NY, pp. 563-608, 1980).

Once the vector or nucleic acid molecule containing the construct(s) hasbeen prepared for expression, the DNA construct(s) may be introducedinto an appropriate host cell by any of a variety of suitable means,i.e., transformation, transfection, conjugation, protoplast fusion,electroporation, particle gun technology, DEAE-dextran-mediatedtransfection, lipofection, calcium phosphate-precipitation, directmicroinjection, and the like. Suitable methods for transforming ortransfecting host cells can be-found in Sambrook, et al. (2001). Afterthe introduction of the vector, recipient cells are grown in a selectivemedium, which selects for the growth of vector-containing cells.Expression of the cloned gene(s) results in the production of a proteinof interest, or fragments thereof.

For other suitable expression systems for both prokaryotic andeukaryotic cells see Sambrook, et al, “Molecular Cloning: A LaboratoryManual,” 3rd ed., Cold Spring Harbor Laboratory, Cold Spring HarborLaboratory Press, Cold Spring Harbor, N.Y., 2001, which is-herebyincorporated by reference in its entirety, including any drawings,figures, and tables.

For transformation of eukaryotic cells, it is known that, depending uponthe expression vector and transfection technique used, only a smallfraction of cells may integrate the foreign DNA into their genome. Inorder to identify and select these integrants, a gene that encodes aselectable marker (e.g., resistance to antibiotics) is generallyintroduced into the host cells along with the gene of interest.Preferred selectable markers include those which confer resistance todrugs, such as G418, hygromycin, neomycin, methotrexate, glyphosate, andbialophos. Nucleic acid encoding a selectable marker can be introducedinto a host cell on the same vector as that encoding the protein ofinterest or can be introduced on a separate vector. Cells stablytransformed with the introduced nucleic acid can be identified by drugselection (e.g., cells that have incorporated the selectable marker genewill survive, while the other cells die).

A host cell of the invention, such as a prokaryotic or eukaryotic hostcell in culture, can be used to produce (i.e., express) the protein ofinterest. Accordingly, the invention further provides methods forproducing the protein of interest using the host cells of the invention.In one embodiment, the method comprises culturing the host cell intowhich a recombinant expression vector encoding the protein of interesthas been introduced in a suitable medium such that the protein ofinterest is produced, and may be purified by one skilled in the art.

In some aspects of the chemokine analogs of the invention, the analogscontain a linker, having the denoted structure [linker] (shown in bold),wherein the linker has the following structure: H₂N—Z_(A)—COOH asdefined below.

IL-8 Compounds

In one aspect of this invention, the chemokine analogs contain linearIL-8 analogs of the present invention corresponding to a portion of theN-terminal of IL-8 having the following structures: IL-8-1(1-15) acid oramide a1) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:9)Cys-Gln-Cys-Ile-Lys-Thr-Tyr- Ser-Lys-(OH)NH₂ a2)RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:10)Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr- Ser-Lys-(OH)NH₂ a3)RNH-Xaa₃-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:11)Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr- Ser-Lys-(OH)NH₂ a4)RNH-Ser-Xaa₃-Lys-Glu-Leu-Arg- (SEQ ID NO:12)Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr- Ser-Lys-(OH)NH₂ a5)RNH-Ser-Ala-Xaa₃-Glu-Leu-Arg- (SEQ ID NO:13)Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr- Ser-Lys-(OH)NH₂ IL-8-1(1-13) acid oramide a6) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:14)Cys-Gln-Cys-Ile-Lys-Thr-Tyr- (OH)NH₂ a7) RNH-Ser-Ala-Lys-Glu-Leu-Arg-(SEQ ID NO:15) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr- (OH)NH₂ a8)RNH-Xaa₃-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:16)Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr- (OH)NH₂ a9) RNH-Ser-Xaa₃-Lys-Glu-Leu-Arg-(SEQ ID NO:17) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr- (OH)NH₂ a10)RNH-Ser-Ala-Xaa₃-Glu-Leu-Arg- (SEQ ID NO:18)Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr- (OH)NH₂ IL-8-1(1-11) acid or amide a11)RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:19) Cys-Gln-Cys-Ile-Lys-(OH)NH₂a12) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:20)Xaa₁-Gln-Xaa₂-Ile-Lys-(OH)NH₂ a13) RNH-Xaa₃-Ala-Lys-Glu-Leu-Arg- (SEQ IDNO:21) Xaa₁-Gln-Xaa₂-Ile-Lys-(OH)NH₂ a14) RNH-Ser-Xaa₃-Lys-Glu-Leu-Arg-(SEQ ID NO:22) Xaa₁-Gln-Xaa₂-Ile-Lys-(OH)NH₂ a15)RNH-Ser-Ala-Xaa₃-Glu-Leu-Arg- (SEQ ID NO:23)Xaa₁-Gln-Xaa₂-Ile-Lys-(OH)NH₂

Preferred embodiments of linear IL-8 analogs of the present inventioncorresponding to a portion of the intemal-region of IL-8 having thefollowing structures: [A⁹]-IL-8-1(9-33) acid or amide a16)RNH-Ala-Ile-Lys-Thr-Tyr-Ser- (SEQ ID NO:24) Lys-Pro-Phe-His-Pro-Lys-Phe-Ile-Lys-Glu-Leu-Arg-Val-Ile- Glu-Ser-Gly-Pro-His-(OH)NH₂[A³⁴]-IL-8-1(34-49) acid or amide a17) RNH-Ala-Ala-Asn-Thr-Glu-Ile- (SEQID NO:25) Ile-Val-Lys-Leu-Ser-Asp-Gly- Arg-Glu-Leu-(OH)NH₂

Preferred embodiments of linear IL-8 analogs of the present inventioncorresponding to a portion of the C-terminal of IL-8 having thefollowing structures: IL-8-1(51-72) acid or amide a18)RHN-Leu-Asp-Pro-Lys-Glu-Asn- (SEQ ID NO:26) Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-Ser-(OH)NH₂

Preferred embodiments of linear IL-8 analogs of the present inventioncorresponding to a portion of the N-terminal joined with a linker to theC-terninal region of IL-8 having the following structures:IL-8-1(1-15)-[linker]-IL-8-(56-71)-acid or amide a19)RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:27) Cys-Gln-Cys-Ile-Lys-Thr-Tyr-Ser-Lys-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a20) RNH-Ser-Ala-Lys-Glu-Leu-Arg-(SEQ ID NO:28) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr- Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂a22) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:29) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a23)RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:30) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val-Thr-Tyr-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn- (OH)NH₂ a24)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:31) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a25)RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:32) Xaa₁-Gln-Xaa₂-Xaa₂-Lys-Thr-Tyr-Ser-Lys-[linker]-Asn- Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂ a26) RNH-Xaa₃-Ala-Lys-Glu-Leu-(SEQ ID NO:33) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a27) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:34)Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a28) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:35)Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a29) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:36)Xaa₁-Gln-Xaa₂-Ile-Xaa₄-Thr- Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂a30) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:37)Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a31) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:38)Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a32) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:39)Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₁- Thr-Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a33) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:40)Xaa₁-Gln-Xaa₂-Ile-Lys-Xaa₄- Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂a34) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:41) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Xaa₄-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a35)RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:42) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Xaa₄-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a36)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:43) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Xaa₄-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a37)RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:44) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Xaa₄-Ser-Lys-[linker]-Asn- Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂ a38) RNH-Xaa₃-Ala-Lys-Glu-Leu-(SEQ ID NO:45) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Xaa₄-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a39) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:46)Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Xaa₄-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a40) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:47)Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Xaa₄-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a41) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:48)Xaa₁-Gln-Xaa₂-Ile-Lys-Thr- Tyr-Xaa₄-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂a42) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:49) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr-Xaa₄-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a43)RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:50) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr-Xaa₄-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a44)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:51) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr-Xaa₄-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a45)RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:52) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr-Ser-Xaa₄-[linker]-Asn- Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂ a46) RNH-Xaa₃-Ala-Lys-Glu-Leu-(SEQ ID NO:53) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Ser-Xaa₄-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-(OH)NH₂a47) RNH-Ser-Xaa₃-Lys-Glu-Leu-Ar- (SEQ ID NO:54)Xaa₁-Gln-Xaa₂-Ile-Lys-Thr- Tyr-Ser-Xaa₄-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂a48) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:55) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr-Ser-Xaa₄-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂IL-8-1(1-13)-[linker]-IL-8-(56-71)-acid or amide a49)RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:56) Cys-Gln-Cys-Ile-Lys-Thr-Tyr-[linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a50) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ IDNO:57) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr- Tyr-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a51)RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:58) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a52) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQID NO:59) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a53)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:60) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a54) RNH-Ser-Ala-Lys-Glu-Leu-Arg-(SEQ ID NO:61) Xaa₁-Gln-Xaa₂-Xaa₁-Lys-Thr- Tyr-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a55)RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:62) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys-Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a56) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQID NO:63) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a57)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:64) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys-Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu- Asn-(OH)NH₂ a58) RNH-Ser-Ala-Lys-Glu-Leu-(SEQ ID NO:65) ArgXaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a59)RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:66) ArgXaa₁-Gln-Xaa₂-Ile-Xaa₄-Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a60) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQID NO:67) ArgXaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a61)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:68) ArgXaa₁-Gln-Xaa₂-Ile-Xaa₄-Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a62) RNH-Ser-Ala-Lys-Glu-Leu- (SEQID NO:69) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a63)RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:70) ArgXaa₁-Gln-Xaa₂-Ile-Lys-Xaa₄-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a64) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQID NO:71) ArgXaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a65)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:72) ArgXaa₁-Gln-Xaa₂-Ile-Lys-Xaa₄-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a66) RNH-Ser-Ala-Lys-Glu-Leu-Arg-(SEQ ID NO:73) Xaa₁-Gln-Xaa₂--Ile-Lys-Thr- Xaa₁-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a67)RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:74) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Xaa₄-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a68) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQID NO:75) Arg-Xaa₁-Gln-Xaa₂--Ile-Lys- Thr-Xaa₄-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys- Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a69)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:76) Arg-Xaa₁-Gln-Xaa₂--Ile-Lys-Thr-Xaa₄-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂IL-8-1(1-11)-[linker]-IL-8-(56-71)-acid or amide a70)RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:77) Cys-Gln-Cys-Ile-Lys-[linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a71) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ IDNO:78) Xaa₁-Gln-Xaa₂-Ile-Lys- [linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu- Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a72)RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:79) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-[linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a73) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ IDNO:80) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- [linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu- Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a74)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:81) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-[linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a75) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ IDNO:82) Xaa₁-Gln-Xaa₂-Xaa₄-Lys- [linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu- Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a76)RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:83) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys-linker]-Asn-Trp-Val-Gln-Arg- Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a77) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:84)Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a78)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:85) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys-linker]-Asn-Trp-Val-Gln-Arg- Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a79) RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:86)Xaa₁-Gln-Xaa₂-Ile-Xaa₄- [linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu- Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a80)RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:87) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄-[linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a81) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ IDNO:88) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- [linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu- Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a82)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:89) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄-[linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂

Preferred embodiments of cyclic IL-8 analogs of the-present inventioncorresponding to a cyclic portion of the N-terminal-region of IL-8having the following structures: [Xaa₅ ¹, Xaa₆ ¹³]-IL-8-1(1-13) cyclic(Xaa₅-Xaa₆) acid or amide a83) RNH-Xaa₅-Ala-Lys-Glu-Leu-Arg- (SEQ IDNO:90) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Xaa₆- (OH)NH₂ a84)RNH-Xaa₅-Xaa₃-Lys-Glu-Leu-Arg- (SEQ ID NO:91)Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Xaa₆- (OH)NH₂ a85)RNH-Xaa₅-Ala-Xaa₃-Glu-Leu-Arg- (SEQ ID NO:92)Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Xaa₆- (OH)NH₂

Preferred embodiments of cyclic IL-8 analogs of the present inventioncorresponding to a cyclic portion of the internal-region of IL-8 havingthe following structures (the underlined residues below are cyclized):[Xaa₅ ⁹, Xaa₆ ³⁴]-IL-8-1(9-34) cyclic (Xaa₅-Xaa₆) acid or amide a86)RNH-Xaa₅-Ile-Lys-Thr-Tyr-Ser- (SEQ ID NO:93)Lys-Pro-Phe-His-Pro-Lys-Phe- Ile-Lys-Glu-Leu-Arg-Val-Ile-Glu-Ser-Gly-Pro-His-Xaa₆- (OH)NH₂ [Xaa₅ ³⁴, Xaa₆ ⁵⁰]-IL-8-1(34-50)cyclic (Xaa₅-Xaa₆) acid or amide a87) RNH-Xaa₅-Ala-Asn-Thr-Glu-Ile- (SEQID NO:94) Ile-Val-Lys-Leu-Ser-Asp-Gly- Arg-Glu-Leu-Xaa₆-(OH)NH₂

Preferred embodiments of cyclic IL-8 analogs of the present inventioncorresponding to a cyclic portion of the C-termninal region of IL-8having the following structures (the underlined residues below arecyclized): [Xaa₅ ⁵⁰, Xaa₆ ⁷²]-IL-8-1(50-72) cyclic (Xaa₅-Xaa₆) acid oramide a88) RNH-Xaa₅-Leu-Asp-Pro-Lys-Glu- (SEQ ID NO:95)Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-Xaa₆-(OH)NH₂ [A⁵⁰]-IL-8-1(50-72) cyclic (Glu63-Lys67) acid oramide a89) RHN-Ala-Leu-Asp-Pro-Lys-Glu- (SEQ ID NO:96)Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-Ser-(OH)NH₂ [A⁵⁰]-IL-8-1(50-72) cyclic (Lys67-Glu70) acid oramide a90) RHN-Ala-Leu-Asp-Pro-Lys-Glu- (SEQ ID NO:97)Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-Ser-(OH)NH₂ [A⁵⁰]-IL-8-1(50-72) cyclic (Lys64-Glu70) acid oramide a91) RHN-Ala-Leu-Asp-Pro-Lys-Glu- (SEQ ID NO:99)Asn-Trp-Val-Gln-Arg-Val-Val- Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-Ser-(OH)NH₂

Preferred embodiments of cyclic IL-8 analogs of the present inventioncorresponding to a portion the N-terminal region joined with a linker toa cyclic portion of the C-terminal region of IL-8 having the followingstructures (the underlined residues below are cyclized):IL-8-1(1-15)-[linker]-IL-8-(56-71)-cyclic (Glu63-Lys67) acid or amidea92) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:100) Arg-Cys-Gln-Cys-Ile-Lys-Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a93)RNH-Ser-Ala-Lys-Glu-Leu-Arg- (SEQ ID NO:101) Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr-Ser-Lys-[linker]-Asn- Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg- Ala-Glu-Asn-(OH)NH₂ a94)RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:102) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a95)RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:103) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a96)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:104) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr-Ser-Lys-[linker]- Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a97)RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:105) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys-Thr-Tyr-Ser-Lys- [linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a98) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ IDNO:106) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a99) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:107)Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a100) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:108)Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a101) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:109)ArgXaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a102) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:110)ArgXaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a103) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:111)ArgXaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a104) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:112)ArgXaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a105) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:113)ArgXaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a106) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:114)ArgXaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-Ser-Lys [linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a107) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:115)ArgXaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a108) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:116)ArgXaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a109) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:117)ArgXaa₁-Gln-Xaa₂-Ile-Lys- Thr-Xaa₄-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a110) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:118)ArgXaa₁-Gln-Xaa₂-Ile-Lys- Thr-Xaa₄-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a111) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:119)ArgXaa₁-Gln-Xaa₂-Ile-Lys- Thr-Xaa₄-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a112) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:120)ArgXaa₁-Gln-Xaa₂-Ile-Lys- Thr-Xaa₄-Ser-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a113) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:121)ArgXaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Xaa₄-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a114) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:122)ArgXaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Xaa₄-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a115) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:123)ArgXaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Xaa₄-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a116) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:124)ArgXaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Xaa₄-Lys-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂ a117) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:125)Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Ser-Xaa₄-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a118) RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:126)Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Ser-Xaa₄-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a119) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:127)Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Ser-Xaa₄-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ a120) RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:128)Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-Ser-Xaa₄-[linker]-Asn-Trp-Val-Gln-Arg-Val- Val-Glu-Lys-Phe-Leu-Lys- Arg-Ala-Glu-Asn-(OH)NH₂ IL-8-1(1-13)-[linker]-IL-8-(56-71)-cyclic (Glu63-Lys67) acid oramide a121) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:129)Arg-Cys-Gln-Cys-Ile-Lys- Thr-Tyr-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a122)RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:130) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a123) RNH-Xaa₃-Ala-Lys-Glu-Leu-(SEQ ID NO:131) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a124)RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ ID NO:132) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a125) RNH-Ser-Ala-Xaa₃-Glu-Leu-(SEQ ID NO:133) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Thr-Tyr-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a126)RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:134) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys-Thr-Tyr-[linker]-Asn- Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg- Ala-Glu-Asn-(OH)NH₂ a127)RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:135) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys-Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a128) RNH-Ser-Xaa₃-Lys-Glu-Leu-(SEQ ID NO:136) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- Thr-Tyr-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a129)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:137) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys-Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a130) RNH-Ser-Ala-Lys-Glu-Leu-(SEQ ID NO:138) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a131)RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:139) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄-Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a132) RNH-Ser-Xaa₃-Lys-Glu-Leu-(SEQ ID NO:140) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- Thr-Tyr-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a133)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:141) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄-Thr-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a134) RNH-Ser-Ala-Lys-Glu-Leu-(SEQ ID NO:142) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Xaa₁-Tyr-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a135)RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:143) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Xaa₄-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a136) RNH-Ser-Xaa₃-Lys-Glu-Leu-(SEQ ID NO:144) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- Xaa₄-Tyr-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a137)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:145) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-Xaa₄-Tyr-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a138) RNH-Ser-Ala-Lys-Glu-Leu-(SEQ ID NO:146) Arg-Xaa₁-Gln-Xaa₂--Ile-Lys- Thr-Xaa₄-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a139)RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:147) Arg-Xaa₁-Gln-Xaa₂--Ile-Lys-Thr-Xaa₄-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a140) RNH-Ser-Xaa₃-Lys-Glu-Leu-(SEQ ID NO:148) Arg-Xaa₁-Gln-Xaa₂--Ile-Lys- Thr-Xaa₄-[linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu- Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂ a141)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:149) Arg-Xaa₁-Gln-Xaa₂--Ile-Lys-Thr-Xaa₄-[linker]-Asn-Trp- Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala- Glu-Asn-(OH)NH₂IL-8-1(1-11)-[linker]-IL-8-(56-71) cyclic (Glu63-Lys67) acid or amidea142 RNH-Ser-Ala-Lys-Glu-Leu- (SEQ ID NO:150) Arg-Cys-Gln-Cys-Ile-Lys-linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a143) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ IDNO:151) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- [linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a144)RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:152) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-[linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a145) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ IDNO:153) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys- [linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a146)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:154) Arg-Xaa₁-Gln-Xaa₂-Ile-Lys-[linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a147) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ IDNO:155) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- [linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a148)RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:156) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys-[linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a149) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ IDNO:157) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys- [linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a150)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:158) Arg-Xaa₁-Gln-Xaa₂-Xaa₄-Lys-[linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a151) RNH-Ser-Ala-Lys-Glu-Leu- (SEQ IDNO:159) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- [linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a152)RNH-Xaa₃-Ala-Lys-Glu-Leu- (SEQ ID NO:160) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄-[linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a153) RNH-Ser-Xaa₃-Lys-Glu-Leu- (SEQ IDNO:161) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄- [linker]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe- Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂ a154)RNH-Ser-Ala-Xaa₃-Glu-Leu- (SEQ ID NO:162) Arg-Xaa₁-Gln-Xaa₂-Ile-Xaa₄-[linker]-Asn-Trp-Val-Gln- Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂

In the above structures:

-   R is selected from the group consisting of hydrogen, alkyl, alkenyl,    alkynyl, alkylcarbonyl, arylcarbonyl, aryl, PEG (polyethyleneglycol)    and any other modifying group.-   Xaa₃ is selected from the group consisting of L-Pro, D-Pro, P* , Btd    and any L- or D-natural and non-natural amino acid.-   Xaa₄ is selected from the group consisting of P* , Btd and any L- or    D-natural amino acid and any non-natural amino acid.-   Xaa₅ is selected from the group consisting of any L- or D-natural    amino acid and any non-natural amino acid with functional side chain    to allow cyclization with Xaa₆.-   Xaa₆ is selected from the group consisting of any L- or D-natural    amino acid and any non-natural amino acid with functional side chain    to allow cyclization with Xaa₅.    -   P* is:        with Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl,        arylcarbonyl, aryl, aryl-hydroxy, and more

A wide variety of amino acid substitutions may be made in polypeptidesequences, such as lysine to glutamnic acid, lysine to aspartic acid,Orn to Glu, Orn to Asp. Moieties other than naturally occurring aminoacids may also be substituted, such as Btd:

-   -   Btd* is:    -   Z=hydrogen, alkyl, alkenyl, alkylcarbonyl, arylcarbonyl, aryl,        aryl-hydroxy, and more

-   Xaa₁ is selected from the group consisting of any L- or D-natural    amino acid and any non-natural amino acid.

Xaa₂ is selected from the group consisting of any L- or D-natural aminoacid and any non-natural amino acid.

The linker is a bifunctional group covalently attached to the N-terminaland C-terminal portions of the analog having the structure:H₂N—Z_(A)—COOH wherein Z_(A) is selected from the group consisting of:(1) alkyl, alkenyl, aralkyl, alkynyl; (2) —(CH₂)_(n)— wherein n is aninteger n=9 to 14; (3) any combination of four natural amino acids ornon-natural amino acids; and (4) —(Gly)₄—.

IP-10 Compounds:

Preferred embodiments of linear IP-10 analogs of the present inventioncorresponding to a portion of N-terminal have the following structures:IP-10-(1-14) acid or amide b1) RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ IDNO:163) Val-Arg-Cys-Thr-Cys-Ile-Ser- Ile-(OH)NH₂ b2)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr- (SEQ ID NO:164) Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-(OH)NH₂ b3) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr- (SEQ ID NO:165)Val-Arg-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-(OH)NH₂ b4)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr- (SEQ ID NO:166) Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-(OH)NH₂ b5) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃- (SEQ ID NO:167)Val-Arg-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-(OH)NH₂ b6)RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ ID NO:168) Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-(OH)NH₂ b7) RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ ID NO:169)Val-Arg-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-(OH)NH₂ IP-10-(1-17) acid oramide b8) RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ ID NO:170)Val-Arg-Cys-Thr-Cys-Ile-Ser- Ile-Ser-Asn-Gln-(OH)NH₂ b9)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr- (SEQ ID NO:171) Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-(OH)NH₂ b10) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr- (SEQ IDNO:172) Val-Arg-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-Ser-Asn-Gln-(OH)NH₂ b11)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr- (SEQ ID NO:173) Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-(OH)NH₂ b12) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃- (SEQ IDNO:174) Val-Arg-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-Ser-Asn-Gln-(OH)NH₂ b13)RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ ID NO:175) Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-(OH)NH₂ b14) RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ IDNO:176) Val-Arg-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln- (OH)NH₂

Preferred embodiments of linear IP-10 analogs of the present inventioncorresponding to a portion of the internal region of IP-10 having thefollowing structures: [A¹¹]-IP-10-(11-35) acid or amide b15)RNH-Ala-Ile-Ser-Ile-Ser-Asn- (SEQ ID NO:177)Gln-Pro-Val-Asn-Pro-Arg-Ser- Leu-Glu-Lys-Leu-Glu-Ile-Ile-Pro-Ala-Ser-Gln-Phe-(OH)NH₂

Preferred embodiments of linear IP-10 analogs of the present inventioncorresponding to a portion of the N-terminal region and the internalregion of IP-10 having the following structures: IP-10-(1-35) acid oramide b16) RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ ID NO:178)Val-Arg-Cys-Thr-Cys-Ile-Ser- Ile-Ser-Asn-Gln-Pro-Val-Asn-Pro-Arg-Ser-Leu-Glu-Lys-Leu- Glu-Ile-Ile-Pro-Ala-Ser-Gln- Phe-(OH)NH₂b17) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:179)Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln-Pro-Val-Asn-Pro-Arg-Ser-Leu-Glu- Lys-Leu-Glu-Ile-Ile-Pro-Ala-Ser-Gln-Phe-(OH)NH₂ b18) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:180)Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln-Pro-Val-Asn-Pro-Arg-Ser-Leu-Glu- Lys-Leu-Glu-Ile-Ile-Pro-Ala-Ser-Gln-Phe-(OH)NH₂ b19) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:181)Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln-Pro-Val-Asn-Pro-Arg-Ser-Leu-Glu- Lys-Leu-Glu-Ile-Ile-Pro-Ala-Ser-Gln-Phe-(OH)NH₂ b20) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:182)Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln-Pro-Val-Asn-Pro-Arg-Ser-Leu-Glu- Lys-Leu-Glu-Ile-Ile-Pro-Ala-Ser-Gln-Phe-(OH)NH₂ b21) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:183)Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln-Pro-Val-Asn-Pro-Arg-Ser-Leu-Glu- Lys-Leu-Glu-Ile-Ile-Pro-Ala-Ser-Gln-Phe-(OH)NH₂ b22) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:184)Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-Ser-Asn-Gln-Pro-Val-Asn-Pro-Arg-Ser-Leu-Glu- Lys-Leu-Glu-Ile-Ile-Pro-Ala-Ser-Gln-Phe-(OH)NH₂ b23) RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ ID NO:185)Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-Ser-Asn-Gln-Pro-Val-Asn-Pro-Arg-Ser-Leu-Glu-Lys- Leu-Glu-Ile-Ile-Pro-Ala-Ser-Gln-Phe-(OH)NH₂ b24) RNH-Val-Pro-Leu-Ser-Arg-Thr- (SEQ ID NO:186)Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile- Ser-Ile-Ser-Asn-Gln-Pro-Val-Asn-Pro-Arg-Ser-Leu-Glu-Lys- Leu-Glu-Ile-Ile-Pro-Ala-Ser-Gln-Phe-(OH)NH₂

Preferred embodiments of linear IP-10 analogs of the present inventioncorresponding to a portion of the C-terminal region of IP-10 having thefollowing sequence: IP-10-(53-77) acid or amide b25)RNH-Leu-Asn-Pro-Glu-Ser-Lys- (SEQ ID NO:187)Ala-Ile-Lys-Asn-Leu-Leu-Lys- Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂

Preferred embodiments of cyclic IP-10 analogs of the present inventioncorresponding to a portion of the N-termninal region joined with alinker to a cyclic portion of the C-terminal region of IP-10 having thefollowing structures: IP-10-(1-14)-[linker]-IP-10-(65-77)-acid or amideb26) RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:188) Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b27) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ IDNO:189) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b28)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:190) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b29) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ IDNO:191) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b30)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:192) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b31) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ IDNO:193) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b32)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:194) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]- Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser- Pro-(OH)NH₂ b33) RNH-Val-Pro-Leu-Ser-Arg- (SEQID NO:195) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b34)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:196) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b35) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:197) Thr-Val-Arg-Cys-Thr-Cys- Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b36)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:198) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b37) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ IDNO:199) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b38)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:200) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b39) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ IDNO:201) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₅-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b40)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:202) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b41) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:203) XaVal-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b42)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:204) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b43) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:205) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b44)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:206) Thr-Val-Arg-Cys-Thr-Cys-Ile-Xaa₄-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b45) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ IDNO:207) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b46)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:208) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b47) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ IDNO:209) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b48)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:210) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₂-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b49) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ IDNO:211) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b50)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:212) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b51) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:213) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b52)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:214) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b53) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:215) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b54)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:216) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b55) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ IDNO:217) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b56)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:218) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b57) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ IDNO:219) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b58)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:220) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b59) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:221) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b60)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:222) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu- Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b61) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:223) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu- Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂IP-10-(1-14)-[linker]-IP-10-(54-66)-acid or amide b62)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:224) Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b63) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ IDNO:225) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b64)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:226) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b65) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ IDNO:227) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b66)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:228) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b67) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ IDNO:229) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b68)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:230) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b69) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:231) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b70)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:232) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b71) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:233) Thr-Val-Arg-Cys-Thr-Cys- Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b72)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:234) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b73) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ IDNO:235) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b74)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:236) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b75) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ IDNO:237) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b76)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:238) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b77) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:239) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b78)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:240) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b79) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:241) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b80)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:242) Thr-Val-Arg-Cys-Thr-Cys-Ile-Xaa₄-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b81) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ IDNO:243) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b82)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:244) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b83) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ IDNO:245) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b84)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:246) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₂-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b85) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ IDNO:247) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b86)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:248) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b87) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:249) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b88)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:250) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b89) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:251) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b90)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:252) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b91) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ IDNO:253) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b92)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:254) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b93) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ IDNO:255) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b94)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:256) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b95) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:257) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b96)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:258) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu- Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b97) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:259) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala- Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂IP-10-(1-14)-[linker]-IP-10-(59-71)-acid or amide b98)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:260) Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b99) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ IDNO:261) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b100)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:262) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b101) RNH-Val-Pro Xaa₃-Ser-Arg- (SEQ IDNO:263) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b102)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:264) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b103) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ IDNO:265) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b104)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:266) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b105) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:267) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b106)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:268) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b107) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:269) Thr-Val-Arg-Cys-Thr-Cys- Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b108)RH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:270) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b109) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ IDNO:271) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b110)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:272) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b111) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ IDNO:273) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b112)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:274) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b113) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:275) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b114)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:276) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b115) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:277) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b116)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:278) Thr-Val-Arg-Cys-Thr-Cys-Ile-Xaa₄-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b117) RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ IDNO:279) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b118)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:280) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b119) RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ IDNO:281) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b120)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:282) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b121) RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ IDNO:283) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b122)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:284) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b123) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:285) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂- Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b124)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:286) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b125) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:287) Thr-Val-Arg-Cys-Thr-Cys- Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b126)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:288) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b127) RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ IDNO:289) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b128)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:290) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b129) RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ IDNO:291) Thr-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b130)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:292) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b131) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:293) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b132)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:294) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys- Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b133) RNH-Val-Pro-Leu-Ser-Arg- (SEQ IDNO:295) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂- Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu- Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂IP-10-(1-17)-[linker]-IP-10-(65-77)-acid or amide b134)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:296) Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b135)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:297) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b136)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:298) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b137)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:299) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b138)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:300) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b139)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:301) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b140)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:302) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b141)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:303) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b142)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:304) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b143)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:305) Thr-Val-Arg-Cys-Thr-Cys-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro(OH)NH₂ b144)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:306) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b145)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:307) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b146)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:308) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b147)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:309) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b148)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:310) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₅-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b149)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:311) XaVal-Arg-Xaa₁-Thr-Xaa₂-Xaa₁-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b150)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:312) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b151)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:313) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b152)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:314) Thr-Val-Arg-Cys-Thr-Cys-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b153)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:315) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b154)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:316) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b155)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:317) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b156)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:318) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b157)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:319) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b158)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:320) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b159)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:321) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b160)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:322) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b161)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:323) Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b162)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:324) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b163)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:325) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b164)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:326) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b165)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:327) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b166)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:328) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b167)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:329) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b168)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:330) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b169)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:331) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b170)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:332) Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-Ser-Xaa₁-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b171)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:333) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b172)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:334) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b173)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:335) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b174)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:336) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b175)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:337) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b176)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:338) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b177)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:339) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b178)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:340) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b170e)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:341) Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b171e)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:342) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₁- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b172e)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:343) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b173e)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:344) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b174e)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:345) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b175e)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:346) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b176e)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:347) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b177e)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:348) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂ b178e)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:349) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₁- [linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys- Arg-Ser-Pro-(OH)NH₂IP-10-(1-17)-[linker]-IP-10-(54-66)-acid or amide b179)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:350) Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b180)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:351) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b181)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:352) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b182)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:353) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b183)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:354) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b184)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:355) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b185)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:356) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b186)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:357) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b187)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:358) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b188)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:359) Thr-Val-Arg-Cys-Thr-Cys-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b189)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:360) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b190)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:361) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b191)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:362) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b192)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:363) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b193)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:364) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b194)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:365) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b195)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:366) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b196)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:367) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b197)RH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:368) Thr-Val-Arg-Cys-Thr-Cys-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b198)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:369) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b199)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:370) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b200)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:371) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b201)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:372) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b202)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:373) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b203)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:374) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b204)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:375) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b205)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:376) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b206)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:377) Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys(OH)NH₂ b207)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:378) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b208)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:379) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b209)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:380) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b210)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:381) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b211)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:382) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b212)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:383) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b213)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:384) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b214)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:385) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b215)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:386) Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b216)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:387) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b217)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:388) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b218)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:389) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b219)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:390) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b220)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:391) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b221)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:392) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b222)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:393) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b223)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:394) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b224)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:395) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b225)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:396) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b226)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:397) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b227)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:398) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b228)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:399) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b229)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:400) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b230)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:401) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b231)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:402) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂ b232)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:403) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn- Leu-Leu-Lys-(OH)NH₂IP-10-(1-17)-[linker]-IP-10-(59-71)-acid or amide b233)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:404) Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-Ser-Asn-Gln [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b234)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:405) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b235)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:406) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b236)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:407) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b237)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:408) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b238)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:409) Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b239)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:410) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b240)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:411) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b241)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:412) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b242)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:413) Thr-Val-Arg-Cys-Thr-Cys-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b243)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:414) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b244)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:415) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₁-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b245)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:416) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b246)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:417) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b247)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:418) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b248)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:419) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b249)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:420) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b250)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:421) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b251)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:422) Thr-Val-Arg-Cys-Thr-Cys-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b252)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:423) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b253)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:424) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b254)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:425) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b255)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:426) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b256)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:427) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b257)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:428) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b258)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:429) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b259)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:430) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b260)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:431) Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b261)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:432) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b262)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:433) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b263)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO 434) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b264)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:435) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b265)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:436) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b266)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:437) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b267)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:438) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b268)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:439) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b269)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:440) Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b270)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:441) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b271)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:442) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b272)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:443) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b273)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:444) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b274)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:445) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b275)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:446) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b276)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:447) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b277)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:448) Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b278)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:449) Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b279)RNH-Xaa₃-Pro-Leu-Ser-Arg- (SEQ ID NO:450) Thr-Val-Arg-Xaa₁-Th-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b280)RNH-Val-Xaa₃-Leu-Ser-Arg- (SEQ ID NO:451) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b281)RNH-Val-Pro-Xaa₃-Ser-Arg- (SEQ ID NO:452) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b282)RNH-Val-Pro-Leu-Xaa₃-Arg- (SEQ ID NO:453) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b283)RNH-Val-Pro-Leu-Ser-Xaa₃- (SEQ ID NO:454) Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b284)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:455) Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln- Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala- Val-Ser-Lys-Glu-(OH)NH₂ b285)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:456) Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄- [linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val- Ser-Lys-Glu-(OH)NH₂ b286)RNH-Val-Pro-Leu-Ser-Arg- (SEQ ID NO:457) Thr-Val-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln- Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala- Val-Ser-Lys-Glu-(OH)NH₂

Preferred embodiments of cyclic IP-10 analogs of the present inventioncorresponding to a portion the N-terminal region joined with a linker toa cyclic portion of the C-terminal region of IP-10 having the followingstructures (underlined residues are cyclized):IP-10-(1-14)-[linker]-IP-10-(65-77)-cyclic (Glu71- Lys74) acid or amideb287) (SEQ ID NO:458) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b288) (SEQ ID NO:459)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b289) (SEQ ID NO:460)RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b290) (SEQ ID NO:461)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b300) (SEQ ID NO:462)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b301) (SEQ ID NO:463)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro(OH)NH₂ b302) (SEQ ID NO:464)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b303) (SEQ ID NO:465)RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b304) (SEQ ID NO:466)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b305) (SEQ ID NO:467)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b306) (SEQ ID NO:468)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b307) (SEQ ID NO:469)RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b308) (SEQ ID NO:470)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b309) (SEQ ID NO:471)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b310) (SEQ ID NO:472)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b311) (SEQ ID NO:473)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b312) (SEQ ID NO:474)RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b313) (SEQ ID NO:475)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b314) (SEQ ID NO:476)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b315) (SEQ ID NO:477)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b316) (SEQ ID NO:478)RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b317) (SEQ ID NO:479)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b318) (SEQ ID NO:480)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b319) (SEQ ID NO:481)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b320) (SEQ ID NO:482)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b321) (SEQ ID NO:483)RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b322) (SEQ ID NO:484)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b323) (SEQ ID NO:485)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b324) (SEQ ID NO:486)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b325) (SEQ ID NO:487)RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b326) (SEQ ID NO:488)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b327) (SEQ ID NO:489)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b328) (SEQ ID NO:490)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b329) (SEQ ID NO:491)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b330) (SEQ ID NO:492)RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b331) (SEQ ID NO:493)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂IP-10-(1-17)-[linker]-IP-10-(65-77)-cyclic (Glu71- Lys74) acid or amideb332) (SEQ ID NO:494) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b333) (SEQ ID NO:495)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b334) (SEQ ID NO:496)RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b335) (SEQ ID NO:497)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b336) (SEQ ID NO:498)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b337) (SEQ ID NO:499)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b338) (SEQ ID NO:500)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b339) (SEQ ID NO:501)RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b340) (SEQ ID NO:502)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b341) (SEQ ID NO:503)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b342) (SEQ ID NO:504)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b343) (SEQ IDNO:505) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b344) (SEQ IDNO:506) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b345) (SEQ IDNO:507) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b346) (SEQ IDNO:508) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b347) (SEQ IDNO:509) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b348) (SEQ IDNO:510) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b349) (SEQ IDNO:511) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b350) (SEQ IDNO:512) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b351) (SEQ ID NO:513)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b352) (SEQ ID NO:514)RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b353) (SEQ ID NO:515)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b354) (SEQ ID NO:516)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b355) (SEQ ID NO:517)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b356) (SEQ IDNO:518) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro (OH)NH₂ b357) (SEQ IDNO:519) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b358) (SEQ IDNO:520) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b359) (SEQ IDNO:521) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b360) (SEQ ID NO:522)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b361) (SEQ IDNO:523) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b362) (SEQ IDNO:524) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b363) (SEQ IDNO:525) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b364) (SEQ ID NO:526)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b365) (SEQ IDNO:527) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b366) (SEQ IDNO:528) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b367) (SEQ IDNO:529) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b368) (SEQ IDNO:530) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b369) (SEQ ID NO:531)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b370) (SEQ IDNO:532) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b371) (SEQ IDNO:533) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-ArgXaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b372) (SEQ ID NO:534)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b373) (SEQ IDNO:535) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b374) (SEQ IDNO:536) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b375) (SEQ IDNO:537) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b376) (SEQ IDNO:538) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b377) (SEQ IDNO:539) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-Ser--Gln-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b378) (SEQ ID NO:540)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b379) (SEQ IDNO:541) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro(OH)NH₂ b380) (SEQ ID NO:542)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b381) (SEQ ID NO:543)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b382) (SEQ ID NO:544)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro-(OH)NH₂ b383) (SEQ ID NO:545)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b384) (SEQ IDNO:546) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂ b385) (SEQ IDNO:548) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Lys-Ala-Val-Ser-Lys-Glu-Met-Ser-Lys-Arg-Ser-Pro- (OH)NH₂IP-10-(1-14)-[linker]-IP-10-(54-66)-cyclic(Glu57- Lys62) acid or amideb386) (SEQ ID NO:549) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b387) (SEQ ID NO:550)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b388) (SEQ ID NO:551)RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b389) (SEQ ID NO:552)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b400) (SEQ ID NO:553)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b401) (SEQ ID NO:554)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b402) (SEQ ID NO:555)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b403) (SEQ ID NO:556)RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b404) (SEQ ID NO:557)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b405) (SEQ ID NO:558)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Xaa₄Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b406) (SEQ ID NO:559)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b407) (SEQ ID NO:560)RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b408) (SEQ ID NO:561)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b409) (SEQ ID NO:562)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b410) (SEQ ID NO:563)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b411) (SEQ ID NO:564)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b412) (SEQ ID NO:565)RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b413) (SEQ ID NO:566)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b414) (SEQ ID NO:567)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b415) (SEQ ID NO:568)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b416) (SEQ ID NO:569)RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b417) (SEQ ID NO:570)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b418) (SEQ ID NO:571)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b419) (SEQ ID NO:572)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b420) (SEQ ID NO:573)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b421) (SEQ ID NO:574)RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b422) (SEQ ID NO:575)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b423) (SEQ ID NO:576)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b424) (SEQ ID NO:577)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b425) (SEQ ID NO:578)RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b426) (SEQ ID NO:579)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b427) (SEQ ID NO:580)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b428) (SEQ ID NO:581)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b429) (SEQ ID NO:582)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b430) (SEQ ID NO:583)RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b431) (SEQ ID NO:584)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂IP-10-(1-17)-[linker]-IP-10-(54-66)-cyclic(Glu57- Lys62) acid or amideb432) (SEQ ID NO:585) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b433) (SEQ ID NO:586)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro- Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys(OH)NH₂ b434) (SEQ ID NO:587)RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro- Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b435) (SEQ ID NO:588)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro- Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b436) (SEQ ID NO:589)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro- Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b437) (SEQ ID NO:590)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro- Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b438) (SEQ ID NO:591)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro- Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b439) (SEQ ID NO:592)RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro- Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b440) (SEQ ID NO:593)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro- Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b441) (SEQ ID NO:594)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b442) (SEQ ID NO:595)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b443) (SEQ IDNO:596) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b444) (SEQ IDNO:597) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b445) (SEQ IDNO:598) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b446) (SEQ IDNO:599) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b447) (SEQ IDNO:600) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b448) (SEQ IDNO:601) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b449) (SEQ IDNO:602) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b450) (SEQ IDNO:603) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b451) (SEQ ID NO:604)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b452) (SEQ IDNO:605) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b453) (SEQ IDNO:606) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b454) (SEQ IDNO:607) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b455) (SEQ IDNO:608) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b456) (SEQ IDNO:609) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b457) (SEQ IDNO:610) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b458) (SEQ IDNO:611) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b459) (SEQ IDNO:612) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b460) (SEQ ID NO:613)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b461) (SEQ IDNO:614) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b462) (SEQ IDNO:615) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b463) (SEQ IDNO:616) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b464) (SEQ IDNO:617) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b465) (SEQ IDNO:618) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b466) (SEQ IDNO:619) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b467) (SEQ IDNO:620) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b468) (SEQ IDNO:621) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b469) (SEQ ID NO:622)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b470) (SEQ IDNO:623) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b471) (SEQ IDNO:624) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b472) (SEQ IDNO:625) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b473) (SEQ IDNO:626) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b474) (SEQ IDNO:627) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b475) (SEQ IDNO:628) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b476) (SEQ IDNO:629) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b477) (SEQ IDNO:630) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b478) (SEQ ID NO:631)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b479) (SEQ IDNO:632) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Leu-Asn-Pro- Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b480) (SEQ ID NO:633)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Leu-Asn-Pro- Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b481) (SEQ ID NO:634)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Leu-Asn-Pro- Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b482) (SEQ ID NO:635)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Leu-Asn-Pro- Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-(OH)NH₂ b483) (SEQ ID NO:636)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b484) (SEQ IDNO:637) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂ b485) (SEQ IDNO:638) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Leu-Asn-Pro-Glu-Ser-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys- (OH)NH₂

In some embodiments IP-10 analogs were cyclized by etherificationbetween Lys66 and Ser69 (underlined residues are cyclized).IP-10-(1-14)-[linker]-IP-10-(59-71)-cyclic(Lys66- Ser69) acid or amideb486) (SEQ ID NO:639) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b487) (SEQ ID NO:640)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b488) (SEQ ID NO:641)RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b489) (SEQ ID NO:642)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b490) (SEQ ID NO:643)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b491) (SEQ ID NO:644)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b492) (SEQ ID NO:645)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b493) (SEQ ID NO:646)RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b494) (SEQ ID NO:647)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b495) (SEQ ID NO:648)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b496) (SEQ ID NO:649)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b497) (SEQ ID NO:650)RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b498) (SEQ ID NO:651)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b499) (SEQ ID NO:652)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b500) (SEQ ID NO:653)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b501) (SEQ ID NO:654)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b502) (SEQ ID NO:655)RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b503) (SEQ ID NO:656)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b504) (SEQ ID NO:657)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b505) (SEQ ID NO:658)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b506) (SEQ ID NO:659)RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b507) (SEQ ID NO:660)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b508) (SEQ ID NO:661)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b509) (SEQ ID NO:662)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b510) (SEQ ID NO:663)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b511) (SEQ ID NO:664)RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b512) (SEQ ID NO:665)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b513) (SEQ ID NO:666)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b514) (SEQ ID NO:667)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b515) (SEQ ID NO:668)RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b516) (SEQ ID NO:669)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b517) (SEQ ID NO:670)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b518) (SEQ ID NO:671)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b519) (SEQ ID NO:672)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b520) (SEQ ID NO:673)RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b521) (SEQ ID NO:674)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂IP-10-(1-17)-[linker]-IP-10-(59-71)-cyclic(Lys66- Ser69) acid or amideb522) (SEQ ID NO:675) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b523) (SEQ ID NO:676)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b524) (SEQ ID NO:677)RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b525) (SEQ ID NO:678)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b526) (SEQ ID NO:679)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b527) (SEQ ID NO:680)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b528) (SEQ ID NO:681)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b529) (SEQ ID NO:682)RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b530) (SEQ ID NO:683)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b531) (SEQ ID NO:684)RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b532) (SEQ ID NO:685)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b533) (SEQ IDNO:686) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b534) (SEQ IDNO:687) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Glu-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b535) (SEQ IDNO:688) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b536) (SEQ IDNO:689) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b537) (SEQ IDNO:690) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b538) (SEQ IDNO:691) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b539) (SEQ IDNO:692) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Xaa₄-Ser-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b540) (SEQ IDNO:693) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b541) (SEQ ID NO:694)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b542) (SEQ IDNO:695) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b543) (SEQ IDNO:696) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b544) (SEQ IDNO:697) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b545) (SEQ IDNO:698) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b546) (SEQ IDNO:699) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b547) (SEQ IDNO:700) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b548) (SEQ IDNO:701) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Xaa₄-Ile-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b549) (SEQ IDNO:702) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b550) (SEQ ID NO:703)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b551) (SEQ IDNO:704) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b552) (SEQ IDNO:705) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b553) (SEQ IDNO:706) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b554) (SEQ IDNO:707) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b555) (SEQ IDNO:708) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b556) (SEQ IDNO:709) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b557) (SEQ IDNO:710) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Xaa₄-Ser-Asn-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b558) (SEQ IDNO:711) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b559) (SEQ ID NO:712)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b560) (SEQ IDNO:713) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b561) (SEQ IDNO:714) RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b562) (SEQ IDNO:715) RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b563) (SEQ IDNO:716) RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b564) (SEQ IDNO:717) RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b565) (SEQ IDNO:718) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b566) (SEQ IDNO:719) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Xaa₄-Gln-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b567) (SEQ IDNO:720) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Arg-Cys-Thr-Cys-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b568) (SEQ ID NO:721)RNH-Xaa₃-Pro-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b569) (SEQ IDNO:722) RNH-Val-Xaa₃-Leu-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b570) (SEQ ID NO:723)RNH-Val-Pro-Xaa₃-Ser-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b571) (SEQ ID NO:724)RNH-Val-Pro-Leu-Xaa₃-Arg-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b572) (SEQ ID NO:725)RNH-Val-Pro-Leu-Ser-Xaa₃-Thr-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-GlnXaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu-(OH)NH₂ b573) (SEQ ID NO:726)RNH-Val-Pro-Leu-Ser-Arg-Xaa₃-Val-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b574) (SEQ IDNO:727) RNH-Val-Pro-Leu-Ser-Arg-Thr-Xaa₃-Arg-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂ b575) (SEQ IDNO:728) RNH-Val-Pro-Leu-Ser-Arg-Thr-Val-Xaa₃-Xaa₁-Thr-Xaa₂-Ile-Ser-Ile-Ser-Gln-Xaa₄-[linker]-Lys-Ala-Ile-Lys-Asn-Leu-Leu-Lys-Ala-Val-Ser-Lys-Glu- (OH)NH₂

In the above structures:

-   R is selected from the group consisting of hydrogen, alkyl, alkenyl,    alkynyl, alkylcarbonyl, arylcarbonyl, aryl, PEG (polyethyleneglycol)    and any other modifying group.-   Xaa₃ is selected from the group consisting of L-Pro, D-Pro, P* , Btd    and any L- or D-natural and non-natural amino acid.-   Xaa₄ is selected from the group consisting of P* , Btd and any L- or    D-natural amino acid and any non-natural amino acid.    -   P* is:        with Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl,        arylcarbonyl, aryl, aryl-hydroxy, and more

A wide variety of amino acid substitutions may be made in polypeptidesequences, such as lysine to glutamic acid, lysine to aspartic acid, Ornto Glu, Orn to Asp. Moieties other than naturally occurring amino acidsmay also be substituted, such as Btd:

-   -   Btd* is:    -   Z=hydrogen, alkyl, alkenyl, alkylcarbonyl, arylcarbonyl, aryl,        aryl-hydroxy, and more

-   Xaa₁ is selected from the group consisting of any L- or D-natural    amino acid and any non-natural amino acid.

-   Xaa₂ is selected from the group consisting of any L- or D-natural    amino acid and any non-natural amino acid.

The linker is a bifunctional group covalently attached to the N-terminaland C-terminal portions of the analog having the structure:H₂N—Z_(A)—COOH wherein Z_(A) is selected from the group consisting of:(1) alkyl, alkenyl, aralkyl, alkynyl; (2) —(CH₂)_(n)— wherein n is aninteger n=9 to 14; (3) any combination of four natural amino acids ornon-natural amino acids; and (4) 13 (Gly)₄—.

MIP-1α Compounds:

Preferred embodiments of linear MIP-1α analogs of the present inventioncorresponding to a portion of the N-terminal region of MIP-1α having thefollowing sequence: MIP-1α-(1-9) acid or amide c1) (SEQ ID NO:729)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Ala-(OH)NH₂

Preferred embodiments of linear MIP-1α analogs of the present inventioncorresponding to a portion of the internal region of MIP-1α having thefollowing sequences: [A¹¹]-MIP-1α-(11-31) acid or amide c2) (SEQ IDNO:730) RNH-Ala-Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala-Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ MIP-1α-(33-47) acid oramide c3) (SEQ ID NO:731)RNH-Ser-Lys-Pro-Gly-Val-Ile-Phe-Leu-Thr-Tyr-Arg- Ser-Arg-Gln-Val-(OH)NH₂

Preferred embodiments of linear MIP-1α analogs of the present inventioncorresponding to a portion of the N-terminal and the internal region ofMIP-1α having the following structures: MIP-1α-(1-31) acid or amide c4)(SEQ ID NO:732) RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Cys-Cys-Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala-Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ c5) (SEQ ID NO:733)RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala-Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ c6) (SEQ ID NO:734)RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala-Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ c7) (SEQ ID NO:735)RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala-Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ c8) (SEQ ID NO:736)RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala-Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ c9) (SEQ ID NO:737)RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala-Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ c10) (SEQ ID NO:738)RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala-Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ c11) (SEQ ID NO:739)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala-Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂ c12) (SEQ ID NO:740)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala-Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-(OH)NH₂

Preferred embodiments of linear MIP-1α analogs of the present inventioncorresponding to a portion of the C-terminal region of MIP-1α having thefollowing structures: MIP-1α-(49-66) acid or amide c13) (SEQ ID NO:741)RNH-Ala-Asp-Pro-Ser-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂

Preferred embodiments of linear MIP-1α analogs of the present inventioncorresponding to a portion of the N-terminal region joined with a linkerto the C-terminal region of MIP-1α having the following structures:MIP-1α-(1-14)-[linker]-MIP-1α-(53-66) acid or amide c14) (SEQ ID NO:742)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Cys-Cys-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c15) (SEQ ID NO:743)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c16) (SEQ ID NO:744)RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c17) (SEQ ID NO:745)RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c18) (SEQ ID NO:746)RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c19) (SEQ ID NO:747)RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c20) (SEQ ID NO:748)RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c21) (SEQ ID NO:749)RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c22) (SEQ ID NO:750)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c23) (SEQ ID NO:751)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c24) (SEQ ID NO:752)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c25) (SEQ ID NO:753)RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c26) (SEQ ID NO:754)RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c27) (SEQ ID NO:755)RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c28) (SEQ ID NO:756)RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c29) (SEQ ID NO:757)RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c30) (SEQ ID NO:758)RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c31) (SEQ ID NO:759)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c32) (SEQ ID NO:760)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c33) (SEQ ID NO:761)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c34) (SEQ ID NO:762)RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c35) (SEQ ID NO:763)RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c36) (SEQ ID NO:764)RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c37) (SEQ ID NO:765)RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c38) (SEQ ID NO:766)RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c39) (SEQ ID NO:767)RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c40) (SEQ ID NO:768)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c41) (SEQ ID NO:769)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c42) (SEQ ID NO:770)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c43) (SEQ ID NO:771)RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c44) (SEQ ID NO:772)RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c45) (SEQ ID NO:773)RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c46) (SEQ ID NO:774)RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c47) (SEQ ID NO:775)RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c48) (SEQ ID NO:776)RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c49) (SEQ ID NO:777)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c50) (SEQ ID NO:778)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c51) (SEQ ID NO:779)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c52) (SEQ ID NO:780)RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c53) (SEQ ID NO:781)RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c54) (SEQ ID NO:782)RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c55) (SEQ ID NO:783)RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c56) (SEQ ID NO:784)RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c57) (SEQ ID NO:785)RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c58) (SEQ ID NO:786)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c59) (SEQ ID NO:787)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Gln-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂

In some preferred embodiments, glutamine (Gln57) of MIP-1α analogs wasreplaced by lysine (Lys). MIP-1α-(1-14)-[linker]-[K57]-MIP-1α-(53-66)acid or amide c60) (SEQ ID NO:788)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Cys-Cys-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c61) (SEQ ID NO:789)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c62) (SEQ ID NO:790)RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c63) (SEQ ID NO:791)RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c64) (SEQ ID NO:792)RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c65) (SEQ ID NO:793)RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c66) (SEQ ID NO:794)RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c67) (SEQ ID NO:795)RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c68) (SEQ ID NO:796)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c69) (SEQ ID NO:797)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c70) (SEQ ID NO:798)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c71) (SEQ ID NO:799)RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c72) (SEQ ID NO:800)RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c73) (SEQ ID NO:801)RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c74) (SEQ ID NO:802)RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c75) (SEQ ID NO:803)RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c76) (SEQ ID NO:804)RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c77) (SEQ ID NO:805)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c78) (SEQ ID NO:806)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c79) (SEQ ID NO:807)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c80) (SEQ ID NO:808)RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c81) (SEQ ID NO:809)RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c82) (SEQ ID NO:810)RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c83) (SEQ ID NO:811)RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c84) (SEQ ID NO:812)RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c85) (SEQ ID NO:813)RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c86) (SEQ ID NO:814)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c87) (SEQ ID NO:815)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c88) (SEQ ID NO:816)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c89) (SEQ ID NO:817)RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c90) (SEQ ID NO:818)RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c91) (SEQ ID NO:819)RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c92) (SEQ ID NO:820)RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c93) (SEQ ID NO:821)RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c94) (SEQ ID NO:822)RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c95) (SEQ ID NO:823)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c96) (SEQ ID NO:824)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c97) (SEQ ID NO:825)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c98) (SEQ ID NO:826)RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c99) (SEQ ID NO:827)RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c100) (SEQ ID NO:828)RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c101 (SEQ ID NO:829)RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c102) (SEQ ID NO:830)RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c103) (SEQ ID NO:831)RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c104) (SEQ ID NO:832)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c105) (SEQ ID NO:833)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂

Preferred embodiments of cyclic MIP-1α analogs of the present inventioncorresponding to a cyclic portion of the internal region of MIP-1αhaving the following structures: [A¹⁰]-MIP-1α-(10-32) cyclic(Cys11-Cys32) acid or amide c106) (SEQ ID NO:834)RNH-Ala-Cys-Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala-Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-Cys- (OH)NH₂[A¹⁰,K¹¹,E³²]-MIP-1α-(10-32) cyclic (Lys11-Glu32) acid or amide c107)(SEQ ID NO:835) RNH-Ala-Lys-Phe-Ser-Tyr-Thr-Ser-Arg-Gln-Ile-Pro-Gln-Asn-Ala-Asp-Tyr-Phe-Glu-Thr-Ser-Ser-Gln-Glu- (OH)NH₂

Preferred embodiments of cyclic MIP-1α analogs of the present inventioncorresponding to a portion of the N-terminal region joined with a linkerto a cyclic the C-terminal region of MIP-1α having the followingstructures: MIP-1α-(1-14)-[linker]-[K⁵⁷]-MIP-1α-(53-66) cyclic(Lys57-Asp61) acid or amide c108) (SEQ ID NO:836)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Cys-Cys-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c109) (SEQ ID NO:837)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c110) (SEQ ID NO:838)RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c111) (SEQ ID NO:839)RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c112) (SEQ ID NO:840)RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c120) (SEQ ID NO:841)RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c121) (SEQ ID NO:842)RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c122) (SEQ ID NO:843)RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c123) (SEQ ID NO:844)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c124) (SEQ ID NO:845)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c125) (SEQ ID NO:846)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c126) (SEQ ID NO:847)RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c127) (SEQ ID NO:848)RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c128) (SEQ ID NO:849)RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c129) (SEQ ID NO:850)RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c130) (SEQ ID NO:851)RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c131) (SEQ ID NO:852)RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c132) (SEQ ID NO:853)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c133) (SEQ ID NO:854)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂-Xaa₄-Ser-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c134) (SEQ ID NO:855)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c135) (SEQ ID NO:856)RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c136) (SEQ ID NO:857)RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c137) (SEQ ID NO:858)RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c138) (SEQ ID NO:859)RNH-Ser-Leu-Ala-Xaa₁-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c139) (SEQ ID NO:860)RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c140) (SEQ ID NO:861)RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c141) (SEQ ID NO:862)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c142) (SEQ ID NO:863)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c143) (SEQ ID NO:864)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c144) (SEQ ID NO:865)RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c145) (SEQ ID NO:866)RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c146) (SEQ ID NO:867)RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c147) (SEQ ID NO:868)RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c148) (SEQ ID NO:869)RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c149) (SEQ ID NO:870)RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c150) (SEQ ID NO:871)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c151) (SEQ ID NO:872)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Thr-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c152) (SEQ ID NO:873)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c153) (SEQ ID NO:874)RNH-Xaa₃-Leu-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c154) (SEQ ID NO:875)RNH-Ser-Xaa₃-Ala-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c155) (SEQ ID NO:876)RNH-Ser-Leu-Xaa₃-Ala-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c156) (SEQ ID NO:877)RNH-Ser-Leu-Ala-Xaa₃-Asp-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c157) (SEQ ID NO:878)RNH-Ser-Leu-Ala-Ala-Xaa₃-Thr-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c158) (SEQ ID NO:879)RNH-Ser-Leu-Ala-Ala-Asp-Xaa₃-Pro-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c159) (SEQ ID NO:880)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Xaa₃-Thr-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂ c160) (SEQ ID NO:881)RNH-Ser-Leu-Ala-Ala-Asp-Thr-Pro-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Tyr-Xaa₄-[linker]-Glu-Glu-Trp-Val-Lys-Tyr-Val-Asp-Asp-Leu-Glu-Leu-Ser-Ala-(OH)NH₂

In the above structures:

-   R is selected from the group consisting of hydrogen, alkyl, alkenyl,    alkynyl, alkylcarbonyl, arylcarbonyl, aryl, PEG (polyethyleneglycol)    and any other modifying group.-   Xaa₃ is selected from the group consisting of L-Pro, D-Pro, P* , Btd    and any L- or D-natural and non-natural amino acid.-   Xaa₄ is selected from the group consisting of P* , Btd and any L- or    D-natural amino acid and any non-natural amino acid.    -   P* is:        with Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl,        arylcarbonyl, aryl, aryl-hydroxy, and more

A wide variety of amino acid substitutions may be made in polypeptidesequences, such as lysine to glutamic acid, lysine to aspartic acid, Ornto Glu, Orn to Asp. Moieties other than naturally occurring amino acidsmay also be substituted, such as Btd:

-   -   Btd* is:    -   Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl,        arylcarbonyl, aryl, aryl-hydroxy, and more

-   Xaa₁ is selected from the group consisting of any L- or D-natural    amino acid and any non-natural amino acid.

-   Xaa₂ is selected from the group consisting of any L- or D-natural    amino acid and any non-natural amino acid.

The linker is a bifunctional group covalently attached to the N-terminaland C-terminal portions of the analog having the structure:H₂N—Z_(A)—COOH wherein Z_(A) is selected from the group consisting of:(1) alkyl, alkenyl, aralkyl, alkynyl; (2) —(CH₂)_(n)— wherein n is aninteger n=9 to 14; (3) any combination of four natural amino acids ornon-natural amino acids; and (4) —(gly)₄—.

RANTES Compounds

Preferred embodiments of linear RANTES analogs of the present inventioncorresponding to a portion of the N-terminal region of RANTES having thefollowing structures: RANTES-(1-9) acid or amide d1) (SEQ ID NO:882)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-(OH)NH₂

Preferred embodiments of linear RANTES analogs of the present inventioncorresponding to a portion of the internal region of RANTES having thefollowing structures: [A¹¹]-RANTES-(11-33) acid or amide d2) (SEQ IDNO:883) RNH-Ala-Phe-Ala-Tyr-Ile-Ala-Arg-Pro-Leu-Pro-Arg-Ala-His-Ile-Lys-Glu-Tyr-Phe-Tyr-Thr-Ser-Gly-Lys- (OH)NH₂ RANTES-(35-49)acid or amide d3) (SEQ ID NO:884)RNH-Ser-Asn-Pro-Ala-Val-Val-Phe-Val-Thr-Arg-Lys- Asn-Arg-Gln-Val-(OH)NH₂

Preferred embodiments of linear RANTES analogs of the present inventioncorresponding to a portion of the N-terminal and a portion the internalregion of RANTES having the following structures: RANTES-(1-33) acid oramide d4) (SEQ ID NO:885)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys-Phe-Ala-Tyr-Ile-Ala-Arg-Pro-Leu-Pro-Arg-Ala-His-Ile-Lys-Glu-Tyr-Phe-Tyr-Thr-Ser-Gly-Lys-(OH)NH₂

Preferred embodiments of linear RANTES analogs of the present inventioncorresponding to a portion of the C-terminal region of RANTES having thefollowing structures: RANTES-(51-68) acid or amide d5) (SEQ ID NO:886)RNH-Ala-Asn-Pro-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂

Preferred embodiments of linear RANTES analogs of the present inventioncorresponding to a portion of the N-terminal region joined with a linkerto the C-terminal region of RANTES having the following structures:RANTES-(1-14)-[linker]-RANTES-(54-68) acid or amide d6) (SEQ ID NO:887)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d7) (SEQ ID NO:888)RNH-Xaa₃-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d8) (SEQ ID NO:889)RNH-Ser-Xaa₃-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d9) (SEQ ID NO:890)RNH-Ser-Pro-Xaa₃-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d10) (SEQ ID NO:891)RNH-Ser-Pro-Tyr-Xaa₃-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d11) (SEQ ID NO:892)RNH-Ser-Pro-Tyr-Ser-Xaa₃-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d12) (SEQ ID NO:893)RNH-Ser-Pro-Tyr-Ser-Ser-Xaa₃-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d13) (SEQ ID NO:894)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Xaa₃-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d14) (SEQ ID NO:895)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Xaa₃-Pro-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d15) (SEQ ID NO:896)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Xaa₃-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d16) (SEQ ID NO:897)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d17) (SEQ ID NO:898)RNH-Xaa₃-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d18) (SEQ ID NO:899)RNH-Ser-Xaa₃-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d19) (SEQ ID NO:900)RNH-Ser-Pro-Xaa₃-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d20) (SEQ ID NO:901)RNH-Ser-Pro-Tyr-Xaa₃-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d21) (SEQ ID NO:902)RNH-Ser-Pro-Tyr-Ser-Xaa₃-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d22) (SEQ ID NO:903)RNH-Ser-Pro-Tyr-Ser-Ser-Xaa₃-Thr-Thr-Pro-Xaa₁-Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d23) (SEQ ID NO:904)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Xaa₃-Thr-Pro-Xaa₁-Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d24) (SEQ ID NO:905)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Xaa₃-Pro-Xaa₁-Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d25) (SEQ ID NO:906)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Xaa₃-Xaa₁-Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d26) (SEQ ID NO:907)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d27) (SEQ ID NO:908)RNH-Xaa₃-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d28) (SEQ ID NO:909)RNH-Ser-Xaa₃-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d29) (SEQ ID NO:910)RNH-Ser-Pro-Xaa₃-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d30) (SEQ ID NO:911)RNH-Ser-Pro-Tyr-Xaa₃-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d31) (SEQ ID NO:912)RNH-Ser-Pro-Tyr-Ser-Xaa₃-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d32) (SEQ ID NO:913)RNH-Ser-Pro-Tyr-Ser-Ser-Xaa₃-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d33) (SEQ ID NO:914)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Xaa₃-Thr-Pro-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d34) (SEQ ID NO:915)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Xaa₃-Pro-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d35) (SEQ ID NO:916)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Xaa₃-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d36) (SEQ ID NO:917)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d37) (SEQ ID NO:918)RNH-Xaa₃-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d38) (SEQ ID NO:919)RNH-Ser-Xaa₃-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d39) (SEQ ID NO:920)RNH-Ser-Pro-Xaa₃-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Xaa₁-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d40) (SEQ ID NO:921)RNH-Ser-Pro-Tyr-Xaa₃-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d41) (SEQ ID NO:922)RNH-Ser-Pro-Tyr-Ser-Xaa₃-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Xaa₁-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d42) (SEQ ID NO:923)RNH-Ser-Pro-Tyr-Ser-Ser-Xaa₃-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d43) (SEQ ID NO:924)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Xaa₃-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d44) (SEQ ID NO:925)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Xaa₃-Pro-Xaa₁-Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d45) (SEQ ID NO:926)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Xaa₃-Xaa₁-Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂

Preferred embodiments of cyclic RANTES analogs of the present inventioncorresponding to cyclic a portion of the internal region of RANTEShaving the following structures: [Ala¹⁰]-RANTES-(10-34)cyclic(Cys11-Cys34) acid or amide d46) (SEQ ID NO:927)RNH-Ala-Cys-Phe-Ala-Tyr-Ile-Ala-Arg-Pro-Leu-Pro-Arg-Ala-His-Ile-Lys-Glu-Tyr-Phe-Tyr-Thr-Ser-Gly- Lys-Cys-(OH)NH₂[Glu¹⁰]-RANTES-(10-33) cyclic(Glu11-Lys33) acid or amide d47) (SEQ IDNO:928) RNH-Glu-Cys-Phe-Ala-Tyr-Ile-Ala-Arg-Pro-Leu-Pro-Arg-Ala-His-Ile-Lys-Glu-Tyr-Phe-Tyr-Thr-Ser-Gly- Lys-(OH)NH₂[Ala¹⁰]-RANTES-(10-34) cyclic(Glu26-Lys33) acid or amide d48) (SEQ IDNO:929) RNH-Ala-Cys-Phe-Ala-Tyr-Ile-Ala-Arg-Pro-Leu-Pro-Arg-Ala-His-Ile-Lys-Glu-Tyr-Phe-Tyr-Thr-Ser-Gly- Lys-(OH)NH₂

Preferred embodiments of cyclic RANTES analogs of the present inventioncorresponding to the N-terminal region and a cyclic a portion of theinternal region of RANTES having the following structures: RANTES-(1-33)cyclic(Glu26-Lys33) acid or amide d49) (SEQ ID NO:930)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys-Phe-Ala-Tyr-Ile-Ala-Arg-Pro-Leu-Pro-Arg-Ala-His-Ile-Lys-Glu-Tyr-Phe-Tyr-Thr-Ser-Gly-Lys-(OH)NH₂ d50) (SEQ ID NO:931)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Tyr-Ile-Ala-Arg-Pro-Leu-Pro-Arg-Ala-His-Ile-Lys-Glu-Tyr-Phe-Tyr-Thr-Ser-Gly-Lys-(OH)NH₂

Preferred embodiments of cyclic RANTES analogs of the present inventioncorresponding to a portion of the N-terminal region joined with a linkerto cyclic portion of the C-terminal region of RANTES having thefollowing structures: RANTES-(1-14)-[linker]-RANTES-(54-68) cyclic(Lys56-Glu60) acid or amide d51) (SEQ ID NO:932)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d52) (SEQ ID NO:933)RNH-Xaa₃-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d53) (SEQ ID NO:934)RNH-Ser-Xaa₃-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d54) (SEQ ID NO:935)RNH-Ser-Pro-Xaa₃-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d55) (SEQ ID NO:936)RNH-Ser-Pro-Tyr-Xaa₃-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d56) (SEQ ID NO:937)RNH-Ser-Pro-Tyr-Ser-Xaa₃-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d57) (SEQ ID NO:938)RNH-Ser-Pro-Tyr-Ser-Ser-Xaa₃-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser(OH)NH₂ d58) (SEQ ID NO:939)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Xaa₃-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d59) (SEQ ID NO:940)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Xaa₃-Pro-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d60) (SEQ ID NO:941)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Xaa₃-Xaa₁-Xaa₂-Phe-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d61) (SEQ ID NO:942)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d62) (SEQ ID NO:943)RNH-Xaa₃-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d63) (SEQ ID NO:944)RNH-Ser-Xaa₃-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d64) (SEQ ID NO:945)RNH-Ser-Pro-Xaa₃-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Xaa₁-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d65) (SEQ ID NO:946)RNH-Ser-Pro-Tyr-Xaa₃-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d66) (SEQ ID NO:947)RNH-Ser-Pro-Tyr-Ser-Xaa₃-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d67) (SEQ ID NO:948)RNH-Ser-Pro-Tyr-Ser-Ser-Xaa₃-Thr-Thr-Pro-Xaa₁-Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d68) (SEQ ID NO:949)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Xaa₃-Thr-Pro-Xaa₁-Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d69) (SEQ ID NO:950)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Xaa₃-Pro-Xaa₁-Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d70) (SEQ ID NO:951)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Xaa₃-Xaa₁-Xaa₂-Xaa₄-Ala-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d71) (SEQ ID NO:952)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d72) (SEQ ID NO:953)RNH-Xaa₃-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d73) (SEQ ID NO:954)RNH-Ser-Xaa₃-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d74) (SEQ ID NO:955)RNH-Ser-Pro-Xaa₃-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d75) (SEQ ID NO:956)RNH-Ser-Pro-Tyr-Xaa₃-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d76) (SEQ ID NO:957)RNH-Ser-Pro-Tyr-Ser-Xaa₃-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d77) (SEQ ID NO:958)RNH-Ser-Pro-Tyr-Ser-Ser-Xaa₃-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d78) (SEQ ID NO:959)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Xaa₃-Thr-Pro-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d79) (SEQ ID NO:960)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Xaa₃-Pro-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d80) (SEQ ID NO:961)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Xaa₃-Xaa₁-Xaa₂-Phe-Xaa₄-Tyr-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d81) (SEQ ID NO:962)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Cys-Cys-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d82) (SEQ ID NO:963)RNH-Xaa₃-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d83) (SEQ ID NO:964)RNH-Ser-Xaa₃-Tyr-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d84) (SEQ ID NO:965)RNH-Ser-Pro-Xaa₃-Ser-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d85) (SEQ ID NO:966)RNH-Ser-Pro-Tyr-Xaa₃-Ser-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d86) (SEQ ID NO:967)RNH-Ser-Pro-Tyr-Ser-Xaa₃-Asp-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Xaa₁-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d87) (SEQ ID NO:968)RNH-Ser-Pro-Tyr-Ser-Ser-Xaa₃-Thr-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d88) (SEQ ID NO:969)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Xaa₃-Thr-Pro-Xaa₁-Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d89) (SEQ ID NO:970)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Xaa₃-Pro-Xaa₁-Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂ d90) (SEQ ID NO:971)RNH-Ser-Pro-Tyr-Ser-Ser-Asp-Thr-Thr-Xaa₃-Xaa₁-Xaa₂-Phe-Ala-Xaa₄-[linker]-Glu-Lys-Lys-Trp-Val-Arg-Glu-Tyr-Ile-Asn-Ser-Leu-Glu-Met-Ser-(OH)NH₂

In the above structures:

-   R is selected from the group consisting of hydrogen, alkyl, alkenyl,    alkynyl, alkylcarbonyl, arylcarbonyl, aryl, PEG (polyethyleneglycol)    and any other modifying group.-   Xaa₃ is selected from the group consisting of L-Pro, D-Pro, P* , Btd    and any L- or D-natural and non-natural amino acid.-   Xaa₄ is selected from the group consisting of P* , Btd and any L- or    D-natural amino acid and any non-natural amino acid.    -   P* is:        with Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl,        arylcarbonyl, aryl, aryl-hydroxy, and more

A wide variety of amino acid substitutions may be made in polypeptidesequences, such as lysine to glutamic acid, lysine to aspartic acid, Ornto Glu, Orn to Asp. Moieties other than naturally occurring amino acidsmay also be substituted, such as Btd:

-   -   Btd* is:    -   Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl,        arylcarbonyl, aryl, aryl-hydroxy, and more

-   Xaa₁ is selected from the group consisting of any L- or D-natural    amino acid and any non-natural amino acid.

-   Xaa₂ is selected from the group consisting of any L- or D-natural    amino acid and any non-natural amino acid.

The linker is a bifunctional group covalently attached to the N-terminaland C-terminal portions of the analog having the structure:H₂N—Z_(A)—COOH wherein Z_(A) is selected from the group consisting of:(1) alkyl, alkenyl, aralkyl, alkynyl; (2) —(CH₂)_(n)— wherein n is aninteger n=9 to 14; (3) any combination of four natural amino acids ornon-natural amino acids; and (4) —(gly)₄—.

I-309 Compounds

Preferred embodiments of linear I-309 analogs of the present inventioncorresponding to a portion of the N-terminal region of I-309 having thefollowing structures: [Ala¹⁰]-I-309-(1-10) acid or amide e1) (SEQ IDNO:972) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Ala- (OH)NH₂

Preferred embodiments of linear I-309 analogs of the present inventioncorresponding to a portion of the internal region of I-309 having thefollowing structures: [Ala¹¹]-I-309-(11-25) acid or amide e2) (SEQ IDNO:973) RNH-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala-Ile-Leu-(OH)NH₂ [Ala¹¹]-I-309-(11-33) acid or amide e3) (SEQ IDNO:974) RNH-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala-Ile-Leu-Cys-Tyr-Arg-Asn-Thr-Ser-Ser-Ile- (OH)NH₂[A²⁶]-I-309-(26-48) acid or amide e4) (SEQ ID NO:975)RNH-Ala-Tyr-Arg-Asn-Thr-Ser-Ser-Ile-Cys-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu- Ala-(OH)NH₂

Preferred embodiments of linear I-309 analogs of the present inventioncorresponding to a portion of the N-terminal region and a portion of theinternal region of I-309 having the following structures: I-309-(1-25)acid or amide e5) (SEQ ID NO:976)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala- Ile-Leu-(OH)NH₂ e6)(SEQ ID NO:977) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala- Ile-Leu-(OH)NH₂ e7)(SEQ ID NO:978) RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂e8) (SEQ ID NO:979) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂e9) (SEQ ID NO:980) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂e10) (SEQ ID NO:981) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂e11) (SEQ ID NO:982) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂e12) (SEQ ID NO:983) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂e13) (SEQ ID NO:984) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂e14) (SEQ ID NO:985) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂e15) (SEQ ID NO:986) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg- Ala-Ile-Leu-(OH)NH₂

Preferred embodiments of linear I-309 analogs of the present inventioncorresponding to a portion of the C-terminal region of I-309 having thefollowing structures: [Ala³⁴]-I-309-(34-67) acid or amide e16) (SEQ IDNO:987) RNH-Ala-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu-Ala-Cys-Ala-Leu-Asp-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-His- (OH)NH₂[Ala⁴⁹]-I-309-(48-73) acid or amide e17) (SEQ ID NO: 988)RNH-Ala-Ala-Leu-Asp-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-His-Cys-Pro-Ser-Lys-Arg- Lys-(OH)NH₂

Preferred embodiments of linear I-309 analogs of the present inventioncorresponding to a portion the N-terminal region joined with a linker tothe C-terminal region of I-309 having the following structures:I-309-(1-14)-[linker]-I-309-(52-64) acid or amide e18) (SEQ ID NO:989)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e19) (SEQ ID NO:990)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e20) (SEQ ID NO:991)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e21) (SEQ ID NO:992)RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e22) (SEQ ID NO:993)RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e23) (SEQ ID NO:994)RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e25) (SEQ ID NO:995)RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e26) (SEQ ID NO:996)RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e27) (SEQ ID NO:997)RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg(OH)NH₂ e28) (SEQ ID NO:998)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e29) (SEQ ID NO:999)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e30) (SEQ ID NO:1000)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e31) (SEQ ID NO:1001)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e32) (SEQ ID NO:1002)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e33) (SEQ ID NO:1003)RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e34) (SEQ ID NO:1004)RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e35) (SEQ ID NO:1005)RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e36) (SEQ ID NO:1006)RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e37) (SEQ ID NO:1007)RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e38) (SEQ ID NO:1008)RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e39) (SEQ ID NO:1009)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e40) (SEQ ID NO:1010)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e41) (SEQ ID NO:1011)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e42) (SEQ ID NO:1012)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e43) (SEQ ID NO:1013)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e44) (SEQ ID NO:1014)RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e45) (SEQ ID NO:1015)RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e46) (SEQ ID NO:1016)RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e47) (SEQ ID NO:1017)RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e48) (SEQ ID NO:1018)RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e49) (SEQ ID NO:1019)RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e50) (SEQ ID NO:1020)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e51) (SEQ ID NO:1021)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e52) (SEQ ID NO:1022)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e53) (SEQ ID NO:1023)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e54) (SEQ ID NO:1024)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e55) (SEQ ID NO:1025)RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e56) (SEQ ID NO:1026)RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e57) (SEQ ID NO:1027)RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e58) (SEQ ID NO:1028)RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e59) (SEQ ID NO:1029)RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e60) (SEQ ID NO:1030)RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e61) (SEQ ID NO:1031)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg(OH)NH₂ e62) (SEQ ID NO:1032)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂I-309-(1-17)-[linker]-I-309-(52-64) acid or amide e63) (SEQ ID NO:1033)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e64) (SEQ ID NO:1034)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e65) (SEQ ID NO:1035)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e66) (SEQ ID NO:1036)RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e67) (SEQ ID NO:1037)RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e68) (SEQ ID NO:1038)RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e69) (SEQ ID NO:1039)RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e70) (SEQ ID NO:1040)RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e71) (SEQ ID NO:1041)RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg(OH)NH₂ e72) (SEQ ID NO:1042)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e73) (SEQ ID NO:1043)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e74) (SEQ ID NO:1044)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg(OH)NH₂ e75) (SEQ ID NO:1045)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e76) (SEQ ID NO:1046)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e77) (SEQ IDNO:1047) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e78) (SEQ IDNO:1048) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e79) (SEQ IDNO:1049) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e80) (SEQ IDNO:1050) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e81) (SEQ IDNO:1051) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e82) (SEQ IDNO:1052) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e83) (SEQ IDNO:1053) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e84) (SEQ IDNO:1054) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e85) (SEQ IDNO:1055) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e86) (SEQ ID NO:1056)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e87) (SEQ ID NO:1057)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e88) (SEQ IDNO:1058) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e89) (SEQ IDNO:1059) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e90) (SEQ IDNO:1060) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e91) (SEQ IDNO:1061) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e92) (SEQ IDNO:1062) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e93) (SEQ IDNO:1063) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e94) (SEQ IDNO:1064) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e95) (SEQ IDNO:1065) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e96) (SEQ IDNO:1066) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e97) (SEQ ID NO:1067)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e98) (SEQ ID NO:1068)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e99) (SEQ IDNO:1069) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e100 (SEQ IDNO:1070) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e101) (SEQ IDNO:1071) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e102) (SEQ IDNO:1072) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e103) (SEQ IDNO:1073) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e104) (SEQ IDNO:1074) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e105) (SEQ IDNO:1075) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e106) (SEQ IDNO:1076) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e107) (SEQ IDNO:1077) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e108) (SEQ ID NO:1078)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e109) (SEQ ID NO:1079)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e110) (SEQ IDNO:1080) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e111) (SEQ IDNO:1081) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e112) (SEQ IDNO:1082) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e113) (SEQ IDNO:1083) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e114) (SEQ IDNO:1084) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e115) (SEQ IDNO:1085) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e116) (SEQ IDNO:1086) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e117) (SEQ IDNO:1087) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e118) (SEQ IDNO:1088) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e119) (SEQ ID NO:1089)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e120) (SEQ ID NO:1090)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e121) (SEQ IDNO:1091) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e122) (SEQ IDNO:1092) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e123) (SEQ IDNO:1093) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e124) (SEQ IDNO:1094) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e125) (SEQ ID NO:1095)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e126) (SEQ ID NO:1096)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e127) (SEQ IDNO:1097) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e128) (SEQ IDNO:1098) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e129) (SEQ IDNO:1099) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e130) (SEQ IDNO:1100) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e131) (SEQ IDNO:1101) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e132) (SEQ IDNO:1102) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e133) (SEQ IDNO:1103) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e134) (SEQ IDNO:1104) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂[Glu⁵⁷]-I-309-(1-14)-[linker]-[Glu⁵⁷]-I-309- (52-62) acid or amide e135)(SEQ ID NO:1105) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e136) (SEQ ID NO:1106)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e137) (SEQ ID NO:1107)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e138) (SEQ ID NO:1108)RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e139) (SEQ ID NO:1109)RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e140) (SEQ ID NO:1110)RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e141) (SEQ ID NO:1111)RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e142) (SEQ ID NO:1112)RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e143) (SEQ ID NO:1113)RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e144) (SEQ ID NO:1114)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e145) (SEQ ID NO:1115)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e146) (SEQ ID NO:1116)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e147) (SEQ ID NO:1117)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e148) (SEQ ID NO:1118)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e149) (SEQ ID NO:1119)RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e150) (SEQ ID NO:1120)RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e151) (SEQ ID NO:1121)RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e152) (SEQ ID NO:1122)RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e153) (SEQ ID NO:1123)RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e154) (SEQ ID NO:1124)RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e155) (SEQ ID NO:1125)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e156) (SEQ ID NO:1126)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e157) (SEQ ID NO:1127)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e158) (SEQ ID NO:1128)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e159) (SEQ ID NO:1129)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e160) (SEQ ID NO:1130)RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e161) (SEQ ID NO:1131)RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e162) (SEQ ID NO:1132)RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e163) (SEQ ID NO:1133)RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e164) (SEQ ID NO:1134)RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e165) (SEQ ID NO:1135)RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e166) (SEQ ID NO:1136)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e167) (SEQ ID NO:1137)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e168) (SEQ ID NO:1138)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e169) (SEQ ID NO:1139)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e170) (SEQ ID NO:1140)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e171) (SEQ ID NO:1141)RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e172) (SEQ ID NO:1142)RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e173) (SEQ ID NO:1143)RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e174) (SEQ ID NO:1144)RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e175) (SEQ ID NO:1145)RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e176) (SEQ ID NO:1146)RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e177) (SEQ ID NO:1147)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e178) (SEQ ID NO:1148)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂[Glu⁵⁷]-I-309-(1-17)-[linker]-[Glu⁵⁷]-I-309- (52-62) acid or amide e179)(SEQ ID NO:1149) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e180) (SEQ ID NO:1150)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e181) (SEQ ID NO:1151)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e182) (SEQ ID NO:1152)RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e183) (SEQ ID NO:1153)RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e184) (SEQ ID NO:1154)RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e185) (SEQ ID NO:1155)RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e186) (SEQ ID NO:1156)RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e187) (SEQ ID NO:1157)RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e188) (SEQ ID NO:1158)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg(OH)NH₂ e189) (SEQ ID NO:1159)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e190) (SEQ ID NO:1160)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e191) (SEQ ID NO:1161)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e192) (SEQ ID NO:1162)RNH-Xaa₃-Ser-Met-Glu-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e193) (SEQ IDNO:1163) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e194) (SEQ IDNO:1164) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e195) (SEQ IDNO:1165) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e196) (SEQ IDNO:1166) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e197) (SEQ IDNO:1167) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e198) (SEQ IDNO:1168) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e199) (SEQ IDNO:1169) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e200) (SEQ IDNO:1170) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e201) (SEQ IDNO:1171) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e202) (SEQ ID NO:1172)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e203) (SEQ ID NO:1173)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e204) (SEQ IDNO:1174) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e205) (SEQ IDNO:1175) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e206) (SEQ IDNO:1176) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e207) (SEQ IDNO:1177) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e208) (SEQ IDNO:1178) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e209) (SEQ IDNO:1179) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e210) (SEQ IDNO:1180) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e211) (SEQ IDNO:1181) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e213 (SEQ IDNO:1182) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e214) (SEQ ID NO:1183)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Glu-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e215) (SEQ ID NO:1184)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e216) (SEQ IDNO:1185) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e217) (SEQ IDNO:1186) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e218) (SEQ IDNO:1187) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e219) (SEQ IDNO:1188) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e220) (SEQ IDNO:1189) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e221) (SEQ IDNO:1190) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e222) (SEQ IDNO:1191) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e223) (SEQ IDNO:1192) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e224) (SEQ IDNO:1193) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e225) (SEQ ID NO:1194)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e226) (SEQ ID NO:1195)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e227) (SEQ IDNO:1196) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e228) (SEQ IDNO:1197) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e229) (SEQ IDNO:1198) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e230) (SEQ IDNO:1199) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e231) (SEQ IDNO:1200) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e232) (SEQ IDNO:1201) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e233) (SEQ IDNO:1202) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e234) (SEQ IDNO:1203) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e235) (SEQ IDNO:1204) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e236) (SEQ ID NO:1205)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e237) (SEQ ID NO:1206)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e238) (SEQ IDNO:1207) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e239) (SEQ IDNO:1208) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e240) (SEQ IDNO:1209) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e241) (SEQ IDNO:1210) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e242) (SEQ ID NO:1211)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e243) (SEQ ID NO:1212)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e244) (SEQ IDNO:1213) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e245) (SEQ IDNO:1214) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e246) (SEQ IDNO:1215) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e247) (SEQ IDNO:1216) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e248) (SEQ IDNO:1217) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e249) (SEQ IDNO:1218) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e250) (SEQ IDNO:1219) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e251) (SEQ IDNO:1220) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂

Preferred embodiments of cyclic I-309 analogs of the present inventioncorresponding to a cyclic portion of the internal region of I-309 havingthe following structures: [Ala²⁶]-I-309-(26-49) cyclic(Glu37-Lys42) acidor amide e252) (SEQ ID NO:1221)RNH-Ala-Tyr-Arg-Asn-Thr-Ser-Ser-Ile-Cys-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu- Ala-(OH)NH₂[Ala²⁶]-I-309-(26-49) cyclic(Glu37-Lys44) acid or amide e253) (SEQ IDNO:1222) RNH-Ala-Tyr-Arg-Asn-Thr-Ser-Ser-Ile-Cys-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu- Ala-(OH)NH₂[Ala²⁶]-I-309-(26-49) cyclic(Glu37-Lys47) acid or amide e254) (SEQ IDNO:1223) RNH-Ala-Tyr-Arg-Asn-Thr-Ser-Ser-Ile-Cys-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu- Ala-(OH)NH₂

Preferred embodiments of cyclic I-309 analogs of the present inventioncorresponding to a cyclic portion of the N-terminal region and theinternal region of I-309 having the following structures: I-309-(1-25)cyclic(Lys1-Glu18) acid or amide e256) (SEQ ID NO:1224)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala- Ile-Leu-(OH)NH₂ e257)(SEQ ID NO:1225) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala- Ile-Leu-(OH)NH₂I-309-(1-25) cyclic(Lys1-Glu20) acid or amide e258) (SEQ ID NO:1226)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala- Ile-Leu-(OH)NH₂ e259)(SEQ ID NO:1227) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala- Ile-Leu-(OH)NH₂

Preferred embodiments of cyclic I-309 analogs of the present inventioncorresponding to a cyclic portion of the C-terminal region of I-309having the following structures: [Ala³⁴]-I-309-(34-67)cyclic(Glu37-Lys44) acid or amide e260) (SEQ ID NO:1228)RNH-Ala-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu-Ala-Cys-Ala-Leu-Asp-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-His- (OH)NH₂[Ala³⁴]-I-309-(34-67) cyclic(Glu37-Lys44) acid or amide e261) (SEQ IDNO:1229) RNH-Ala-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu-Ala-Cys-Ala-Leu-Asp-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ [Ala³⁴]-I-309-(34-67)cyclic(Glu37-Lys47) acid or amide e262) (SEQ ID NO:1230)RNH-Ala-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu-Ala-Cys-Ala-Leu-Asp-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ [Ala³⁴]-I-309-(34-67)cyclic(Glu37-Lys63) acid or amide e263) (SEQ ID NO:1231)RNH-Ala-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu-Ala-Cys-Ala-Leu-Asp-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg(OH)NH₂ [Ala³⁴]-I-309-(34-67)cyclic(Glu48-Lys63) acid or amide e264) (SEQ ID NO:1232)RNH-Ala-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu-Ala-Cys-Ala-Leu-Asp-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ [Ala³⁴]-I-309-(34-67)cyclic(Lys44-Glu48) acid or amide e265) (SEQ ID NO:1233)RNH-Ala-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu-Ala-Cys-Ala-Leu-Asp-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ [Ala³⁴]-I-309-(34-67)cyclic(Lys42-Glu48) acid or amide e266) (SEQ ID NO:1234)RNH-Ala-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu-Ala-Cys-Ala-Leu-Asp-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂

Preferred embodiments of cyclic I-309 analogs of the present inventioncorresponding to a portion the N-terminal region joined with a linker toa cyclic portion of the C-terminal region of I-309 having the followingstructures (underlined residues are cyclized):[Glu⁵⁷]-I-309-(1-14)-[linker]-[Glu⁵⁷]-I-309- (52-62) cyclic(Glu57-Lys61)acid or amide e267) (SEQ ID NO:1235)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e268) (SEQ ID NO:1236)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e269) (SEQ ID NO:1237)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e270) (SEQ ID NO:1238)RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e271) (SEQ ID NO:1239)RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e272) (SEQ ID NO:1240)RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e273) (SEQ ID NO:1241)RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e274) (SEQ ID NO:1242)RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e275) (SEQ ID NO:1243)RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e276) (SEQ ID NO:1244)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e277) (SEQ ID NO:1245)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e278) (SEQ ID NO:1246)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e279) (SEQ ID NO:1247)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e280) (SEQ ID NO:1248)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e281) (SEQ ID NO:1249)RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e282) (SEQ ID NO:1250)RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e283) (SEQ ID NO:1251)RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₁-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e284) (SEQ ID NO:1252)RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e285) (SEQ ID NO:1253)RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e286) (SEQ ID NO:1254)RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e287) (SEQ ID NO:1255)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e288) (SEQ ID NO:1256)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e289) (SEQ ID NO:1257)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e290) (SEQ ID NO:1258)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e291) (SEQ ID NO:1259)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e292) (SEQ ID NO:1260)RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e293) (SEQ ID NO:1261)RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e294) (SEQ ID NO:1262)RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e295) (SEQ ID NO:1263)RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e296) (SEQ ID NO:1264)RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e297) (SEQ ID NO:1265)RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e298) (SEQ ID NO:1266)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e299) (SEQ ID NO:1267)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e300) (SEQ ID NO:1268)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e301) (SEQ ID NO:1269)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e302) (SEQ ID NO:1270)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e303) (SEQ ID NO:1271)RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e304) (SEQ ID NO:1272)RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e305) (SEQ ID NO:1273)RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e306) (SEQ ID NO:1274)RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e307) (SEQ ID NO:1275)RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e308) (SEQ ID NO:1276)RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e309) (SEQ ID NO:1277)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e310) (SEQ ID NO:1278)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂[Glu⁵⁷]-I-309-(1-17)-[linker]-[Glu⁵⁷]-I-309- (52-62) cyclic(Glu57-Lys61)acid or amide e311) (SEQ ID NO:1279)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e312) (SEQ ID NO:1280)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e313) (SEQ ID NO:1281)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e314) (SEQ ID NO:1282)RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e315) (SEQ ID NO:1283)RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e316) (SEQ ID NO:1284)RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e317) (SEQ ID NO:1285)RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e318) (SEQ ID NO:1286)RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e319) (SEQ ID NO:1287)RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e320) (SEQ ID NO:1288)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e321) (SEQ ID NO:1289)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e322) (SEQ ID NO:1290)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e323) (SEQ ID NO:1291)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e324) (SEQ ID NO:1292)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e325) (SEQ IDNO:1293) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e326) (SEQ IDNO:1294) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e327) (SEQ IDNO:1295) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e328) (SEQ IDNO:1296) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e329) (SEQ IDNO:1297) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e330) (SEQ IDNO:1298) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e331) (SEQ IDNO:1299) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e332) (SEQ IDNO:1300) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Xaa₄-Ser-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e333) (SEQ IDNO:1301) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e334) (SEQ ID NO:1302)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e335) (SEQ ID NO:1303)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e336) (SEQ IDNO:1304) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e337) (SEQ IDNO:1305) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e338) (SEQ IDNO:1306) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e339) (SEQ IDNO:1307) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e340) (SEQ IDNO:1308) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e341) (SEQ IDNO:1309) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e342) (SEQ IDNO:1310) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e343) (SEQ IDNO:1311) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Xaa₄-Phe-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e344) (SEQ IDNO:1312) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e345) (SEQ ID NO:1313)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e346) (SEQ ID NO:1314)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e347) (SEQ IDNO:1315) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e348) (SEQ IDNO:1316) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e349) (SEQ IDNO:1317) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e350) (SEQ IDNO:1318) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e351) (SEQ IDNO:1319) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e352) (SEQ IDNO:1320) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e353) (SEQ IDNO:1321) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e354) (SEQ IDNO:1322) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Xaa₄-Ala-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e355) (SEQ IDNO:1323) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e356) (SEQ ID NO:1324)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e357) (SEQ ID NO:1325)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e358) (SEQ IDNO:1326) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e359) (SEQ IDNO:1327) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e360) (SEQ IDNO:1328) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e361) (SEQ IDNO:1329) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e362) (SEQ IDNO:1330) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e363) (SEQ IDNO:1331) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e364) (SEQ IDNO:1332) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e365) (SEQ IDNO:1333) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Phe-Xaa₄-Glu-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e366) (SEQ IDNO:1334) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e367) (SEQ ID NO:1335)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e368) (SEQ ID NO:1336)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e369) (SEQ IDNO:1337) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e370) (SEQ IDNO:1338) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e371) (SEQ IDNO:1339) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Xaa₄-Gln-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e372) (SEQ IDNO:1340) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Cys-Cys-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e373) (SEQ ID NO:1341)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg-(OH)NH₂ e374) (SEQ ID NO:1342)RNH-Xaa₃-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e375) (SEQ IDNO:1343) RNH-Lys-Xaa₃-Met-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e376) (SEQ IDNO:1344) RNH-Lys-Ser-Xaa₃-Gln-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e377) (SEQ IDNO:1345) RNH-Lys-Ser-Met-Xaa₃-Val-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e378) (SEQ IDNO:1346) RNH-Lys-Ser-Met-Gln-Xaa₃-Pro-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e379) (SEQ IDNO:1347) RNH-Lys-Ser-Met-Gln-Val-Xaa₃-Phe-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e380) (SEQ IDNO:1348) RNH-Lys-Ser-Met-Gln-Val-Pro-Xaa₃-Ser-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e381) (SEQ IDNO:1349) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Xaa₃-Arg-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂ e382) (SEQ IDNO:1350) RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Xaa₃-Xaa₁-Xaa₂-Phe-Ser-Phe-Ala-Glu-Xaa₄-[linker]-Thr-Val-Gly-Trp-Val-Glu-Arg-His-Arg-Lys-Met-Leu-Arg- (OH)NH₂

In the above structures:

-   R is selected from the group consisting of hydrogen, alkyl, alkenyl,    alkynyl, alkylcarbonyl, arylcarbonyl, aryl, PEG (polyethyleneglycol)    and any other modifying group.-   Xaa₃ is selected from the group consisting of L-Pro, D-Pro, P* , Btd    and any L- or D-natural and non-natural amino acid.-   Xaa₄ is selected from the group consisting of P* , Btd and any L- or    D-natural amino acid and any non-natural amino acid.    -   P* is:        with Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl,        arylcarbonyl, aryl, aryl-hydroxy, and more

A wide variety of amino acid substitutions may be made in polypeptidesequences, such as lysine to glutamic acid, lysine to aspartic acid, Ornto Glu, or Orn to Asp. Moieties other than naturally occurring aminoacids may also be substituted, such as Btd:

-   -   Btd* is:    -   Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl,        arylcarbonyl, aryl, aryl-hydroxy, and more

-   Xaa₁ is selected from the group consisting of any L- or D-natural    amino acid and any non-natural amino acid.

-   Xaa₂ is selected from the group consisting of any L- or D-natural    amino acid and any non-natural amino acid.

The linker is a bifunctional group covalently attached to the N-terminaland C-terminal portions of the analog having the structure:H₂N—Z_(A)—COOH wherein Z_(A) is selected from the group consisting of:(1) alkyl, alkenyl, aralkyl, alkynyl; (2) —(CH₂)_(n)— wherein n is aninteger n=9 to 14; (3) any combination of four natural amino acids ornon-natural amino acids; and (4) —(gly)₄—.

MCP-1 Compounds:

Preferred embodiments of linear MCP-1 analogs of the present inventioncorresponding to a portion of the N-terminal and the internal region ofMCP-1 having the following structures:

From the chemokine MCP-1 the following compounds:

Preferred embodiments of linear MCP-1 analogs of the present inventioncorresponding to a portion of the N-terminal and the internal region ofMCP-1 having the following structures: MCP-1-(1-35) acid or amide g2)(SEQ ID NO:1351) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Cys-Cys-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g3) (SEQ IDNO:1352) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g4) (SEQ IDNO:1353) RNH-Xaa₃-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g5) (SEQ IDNO:1354) RNH-Gln-Xaa₃-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g6) (SEQ IDNO:1355) RNH-Gln-Pro-Xaa₃-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g7) (SEQ IDNO:1356) RNH-Gln-Pro-Asp-Xaa₃-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g8) (SEQ IDNO:1357) RNH-Gln-Pro-Asp-Ala-Xaa₃-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g9) (SEQ IDNO:1358) RNH-Gln-Pro-Asp-Ala-Ile-Xaa₃-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g10) (SEQ IDNO:1359) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Xaa₃-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g11) (SEQ IDNO:1360) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Xaa₃-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g12) (SEQ IDNO:1361) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Xaa₃-Thr-Xaa₁-Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g13) (SEQ IDNO:1362) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Xaa₃-Xaa₁-Xaa₂-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂[Glu¹³]-MCP-1-(1-35) acid or amide g14) (SEQ ID NO:1363)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Cys-Cys-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g15) (SEQ IDNO:1364) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g16) (SEQ IDNO:1365) RNH-Xaa₃-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g17) (SEQ IDNO:1366) RNH-Gln-Xaa₃-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g18) (SEQ IDNO:1367) RNH-Gln-Pro-Xaa₃-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g19) (SEQ IDNO:1368) RNH-Gln-Pro-Asp-Xaa₃-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g20) (SEQ IDNO:1369) RNH-Gln-Pro-Asp-Ala-Xaa₃-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g21) (SEQ IDNO:1370) RNH-Gln-Pro-Asp-Ala-Ile-Xaa₃-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g22) (SEQ IDNO:1371) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Xaa₃-Pro-Val-Thr-Xaa₁-Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g23) (SEQ IDNO:1372) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Xaa₃-Val-Thr-Xaa₁-Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g24) (SEQ IDNO:1373) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Xaa₃-Thr-Xaa₁-Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂ g25) (SEQ IDNO:1374) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Xaa₃-Xaa₁-Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂

Preferred embodiments of linear MCP-1 analogs of the present inventioncorresponding to a portion of the internal region of MCP-1 having thefollowing structures: MCP-1-(12-36) acid or amide g26) (SEQ ID NO:1375)RNH-Ala-Lys-Xaa₄-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser- Ser-Lys-Glu-(OH)NH₂MCP-1-(37-51) acid or amide g27) (SEQ ID NO:1376)RNH-Pro-Lys-Glu-Ala-Val-Ile-Phe-Lys-Thr-Ile-Val- Ala-Lys-Glu-Ile-(OH)NH₂

Preferred embodiments of linear MCP-1 analogs of the present inventioncorresponding to a portion of the C-terninal region of MCP-1 having thefollowing structures: MCP-1-(53-76) acid or amide g28) (SEQ ID NO:1377)RNH-Ala-Asp-Pro-Lys-Gln-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂

Preferred embodiments of linear MCP-1 analogs of the present inventioncorresponding to a portion the N-terminal region joined with a linker tothe C-terminal region of MCP-1 having the following structures:MCP-1-(13-35)-[linker]-MCP-1-(58-76) acid or amide g29) (SEQ ID NO:1378)RNH-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ MCP-1-(1-14)-[linker]-MCP-1-(58-76) acid oramide g30) (SEQ ID NO:1379)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Cys-Cys-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g31) (SEQ ID NO:1380)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ MCP-1-(1-14)-[linker]-MCP-1-(58-76)acid or amide g32) (SEQ ID NO:1381)RNH-Xaa₃-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g33) (SEQ ID NO:1382)RNH-Gln-Xaa₃-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g34) (SEQ ID NO:1383)RNH-Gln-Pro-Xaa₃-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g35) (SEQ ID NO:1384)RNH-Gln-Pro-Asp-Xaa₃-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g36) (SEQ ID NO:1385)RNH-Gln-Pro-Asp-Ala-Xaa₃-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g37) (SEQ ID NO:1386)RNH-Gln-Pro-Asp-Ala-Ile-Xaa₃-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g38) (SEQ ID NO:1387)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Xaa₃-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g39) (SEQ ID NO:1388)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Xaa₃-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g40) (SEQ ID NO:1389)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Xaa₃-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g41) (SEQ ID NO:1390)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Xaa₃-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g42) (SEQ ID NO:1391)RNH-Xaa₃-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g43) (SEQ ID NO:1392)RNH-Gln-Xaa₃-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g44) (SEQ ID NO:1393)RNH-Gln-Pro-Xaa₃-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g45) (SEQ ID NO:1394)RNH-Gln-Pro-Asp-Xaa₃-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g46) (SEQ ID NO:1395)RNH-Gln-Pro-Asp-Ala-Xaa₃-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g47) (SEQ ID NO:1396)RNH-Gln-Pro-Asp-Ala-Ile-Xaa₃-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g48) (SEQ ID NO:1397)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Xaa₃-Pro-Val-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g49) (SEQ ID NO:1398)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Xaa₃-Val-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g50) (SEQ ID NO:1399)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Xaa₃-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g51) (SEQ ID NO:1400)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Xaa₃-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g52) (SEQ ID NO:1401)RNH-Xaa₃-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g53) (SEQ ID NO:1402)RNH-Gln-Xaa₃-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g54) (SEQ ID NO:1403)RNH-Gln-Pro-Xaa₃-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g55) (SEQ ID NO:1404)RNH-Gln-Pro-Asp-Xaa₃-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g56) (SEQ ID NO:1405)RNH-Gln-Pro-Asp-Ala-Xaa₃-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g57) (SEQ ID NO:1406)RNH-Gln-Pro-Asp-Ala-Ile-Xaa₃-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g58) (SEQ ID NO:1407)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Xaa₃-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g59) (SEQ ID NO:1408)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Xaa₃-Val-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g60) (SEQ ID NO:1409)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Xaa₃-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g61) (SEQ ID NO:1410)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Xaa₃-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂

Preferred embodiments of cyclic MCP-1 analogs of the present inventioncorresponding to a cyclic portion of the N-terminal and the internalregion of MCP-1 having the following structures: [Ala¹¹, Lys¹²,Glu³⁶]-MCP-1-(11-36) cyclic(Lys12- Glu36) acid or amide g62) (SEQ IDNO:1411) RNH-Ala-Lys-Xaa₃-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser- Ser-Lys-Glu-(OH)NH₂[Ala¹¹, Lys¹², Glu³⁶]-MCP-1-(11-36) cyclic(Lys19- Glu36) acid or amideg63) (SEQ ID NO:1412) RNH-Ala-Lys-Xaa₃-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser- Ser-Lys-Glu-(OH)NH₂[Glu¹³]-MCP-1-(1-35) cyclic(Glu13-Lys19) acid or amide g64) (SEQ IDNO:1413) RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Glu-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys- (OH)NH₂

Preferred embodiments of cyclic MCP-1 analogs of the present inventioncorresponding to a portion the N-terminal region joined with a linker toa cyclic portion of the C-terminal region of MCP-1 having the followingstructures: MCP-1-(1-14)-[linker]-MCP-1-(58-76) cyclic(Asp65- Lys74)acid or amide g65) (SEQ ID NO:1414)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Cys-Cys-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g66) (SEQ ID NO:1415)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ MCP-1-(13-35)-[linker]-MCP-1-(58-76)cyclic(Asp65- Lys74) acid or amide g67) (SEQ ID NO:1416)RNH-Tyr-Asn-Phe-Thr-Asn-Arg-Lys-Ile-Ser-Val-Gln-Arg-Leu-Ala-Ser-Tyr-Arg-Arg-Ile-Thr-Ser-Ser-Lys-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ MCP-1-(1-14)-[linker]-MCP-1-(58-76) cyclic(D65-K74) acid or amide g68) (SEQ ID NO:1417)RNH-Xaa₃-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g69) (SEQ ID NO:1418)RNH-Gln-Xaa₃-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g70) (SEQ ID NO:1419)RNH-Gln-Pro-Xaa₃-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g71) (SEQ ID NO:1420)RNH-Gln-Pro-Asp-Xaa₃-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g72) (SEQ ID NO:1421)RNH-Gln-Pro-Asp-Ala-Xaa₃-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g73) (SEQ ID NO:1422)RNH-Gln-Pro-Asp-Ala-Ile-Xaa₃-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g74) (SEQ ID NO:1423)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Xaa₃-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g75) (SEQ ID NO:1424)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Xaa₃-Val-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g76) (SEQ ID NO:1425)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Xaa₃-Thr-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g77) (SEQ ID NO:1426)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Xaa₃-Xaa₁-Xaa₂-Tyr-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g78) (SEQ ID NO:1427)RNH-Xaa₃-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g79) (SEQ ID NO:1428)RNH-Gln-Xaa₃-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g80) (SEQ ID NO:1429)RNH-Gln-Pro-Xaa₃-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g81) (SEQ ID NO:1430)RNH-Gln-Pro-Asp-Xaa₃-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr(OH)NH₂ (SEQ ID NO:1431) g82)RNH-Gln-Pro-Asp-Ala-Xaa₃-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ (SEQ ID NO:1432) g83)RNH-Gln-Pro-Asp-Ala-Ile-Xaa₃-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ (SEQ ID NO:1433) g84)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Xaa₃-Pro-Val-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g85) (SEQ ID NO:1434)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Xaa₃-Val-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g86) (SEQ ID NO:1435)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Xaa₃-Thr-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g87) (SEQ ID NO:1436)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Xaa₃-Xaa₁-Xaa₂-Xaa₄-Asn-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g88) (SEQ ID NO:1437)RNH-Xaa₃-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g89) (SEQ ID NO:1438)RNH-Gln-Xaa₃-Asp-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g90) (SEQ ID NO:1439)RNH-Gln-Pro-Xaa₃-Ala-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g91) (SEQ ID NO:1440)RNH-Gln-Pro-Asp-Xaa₃-Ile-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g92) (SEQ ID NO:1441)RNH-Gln-Pro-Asp-Ala-Xaa₃-Asn-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g93) (SEQ ID NO:1442)RNH-Gln-Pro-Asp-Ala-Ile-Xaa₃-Ala-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g94) (SEQ ID NO:1443)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Xaa₃-Pro-Val-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g95) (SEQ ID NO:1444)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Xaa₃-Val-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g96) (SEQ ID NO:1445)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Xaa₃-Thr-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂ g97) (SEQ ID NO:1446)RNH-Gln-Pro-Asp-Ala-Ile-Asn-Ala-Pro-Val-Xaa₃-Xaa₁-Xaa₂-Tyr-Xaa₄-[linker]-Lys-Trp-Val-Gln-Asp-Ser-Met-Asp-His-Leu-Asp-Lys-Gln-Thr-(OH)NH₂

In the above structures:

-   R is selected from the group consisting of hydrogen, alkyl, alkenyl,    alkynyl, alkylcarbonyl, arylcarbonyl, aryl, PEG (polyethyleneglycol)    and any other modifying group. p0 Xaa₃ is selected from the group    consisting of L-Pro, D-Pro, P* , Btd and any L- or D-natural and    non-natural amino acid.-   Xaa₄ is selected from the group consisting of P* , Btd and any L- or    D-natural amino acid and any non-natural amino acid.

P* is:

with Z=Ar, Ar—OH, alkyl and more

A wide variety of amino acid substitutions may be made in polypeptidesequences, such as lysine to glutamic acid, lysine to aspartic acid, Ornto Glu, or Orn to Asp. Moieties other than naturally occurring aminoacids may also be substituted, such as Btd:

-   -   Btd* is:    -   Z=Alkyl, Ar, Ar—OH and more

-   Xaa₁ is selected from the group consisting of any L- or D-natural    amino acid and any non-natural amino acid.

-   Xaa₂ is selected from the group consisting of any L- or D-natural    amino acid and any non-natural amino acid.

The linker is a bifunctional group covalently attached to the N-terminaland C-terminal portions of the analog having the structure:H₂N—Z_(A)—COOH wherein Z_(A) is selected from the group consisting of:(1) alkyl, alkenyl, aralkyl, alkynyl; (2) —(CH₂)_(n)— wherein n is aninteger n=9 to 14; (3) any combination of four natural amino acids ornon-natural amino acids; and (4) —(gly)₄—.

CCL28 Compounds

Preferred embodiments of linear CCL28 analogs of the present inventioncorresponding to a portion of the N-terminal region of CCL28 having thefollowing structures: CCL28-(1-7) acid or amide h1) (SEQ ID NO:1447)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Ser-(OH)NH₂ CCL28-(1-26) acid or amide h2)(SEQ ID NO:1448) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Ser-Cys-Cys-Thr-Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu-Arg- Val-Asn-Met-(OH)NH₂ h3)(SEQ ID NO:1449) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu-Arg- Val-Asn-Met-(OH)NH₂ h4)(SEQ ID NO:1450) RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu- Arg-Val-Asn-Met-(OH)NH₂h5) (SEQ ID NO:1451) RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu- Arg-Val-Asn-Met-(OH)NH₂h6) (SEQ ID NO:1452) RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu- Arg-Val-Asn-Met-(OH)NH₂h7) (SEQ ID NO:1453) RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu- Arg-Val-Asn-Met-(OH)NH₂h8) (SEQ ID NO:1454) RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu- Arg-Val-Asn-Met-(OH)NH₂h9) (SEQ ID NO:1455) RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu- Arg-Val-Asn-Met-(OH)NH₂h10) (SEQ ID NO:1456) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu- Arg-Val-Asn-Met-(OH)NH₂

Preferred embodiments of linear CCL28 analogs of the present inventioncorresponding to a portion of the internal region of CCL28 having thefollowing structures: CCL28-(10-26) acid or amide h11) (SEQ ID NO:1457)RNH-Thr-Glu-Val-Ser-His-His-Ile-Ser-Arg-Arg-Leu-Leu-Glu-Arg-Val-Asn-Met-(OH)NH₂ CCL28-(27-49) acid or amide h12) (SEQ IDNO:1458) RNH-Arg-Ile-Gln-Arg-Ala-Asp-Gly-Asp-Cys-Asp-Leu-Ala-Ala-Val-Ile-Leu-His-Val-Lys-Arg-Arg-Arg-Ile- (OH)NH₂ CCL28-(50-74)acid or amide h13) (SEQ ID NO:1459)RNH-Val-Ser-Pro-His-Asn-His-Thr-Val-Lys-Gln-Trp-Met-Lys-Val-Gln-Ala-Ala-Lys-Lys-Asn-Gly-Lys-Gly- Asn-Val-(OH)NH₂

Preferred embodiments of linear CCL28 analogs of the present inventioncorresponding to a portion of the C-terminal region of CCL28 having thefollowing structures: CCL28-(75-102) acid or amide h14) (SEQ ID NO:1460)RNH-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asn-Arg-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂

Preferred embodiments of linear CCL28 analogs of the present inventioncorresponding to a portion the N-terminal region joined with a linker tothe C-terminal region of CCL28 having the following structures:CCL28-(1-14)-[linker]-[Asp⁸⁶]-CCL28-(75-88) acid or amide h15) (SEQ IDNO:1461) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Ser-Cys-Cys-Thr-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h16) (SEQ ID NO:1462)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h17) (SEQ ID NO:1463)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h18) (SEQ ID NO:1464)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h19) (SEQ ID NO:1465)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h20) (SEQ ID NO:1466)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h21) (SEQ ID NO:1467)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h22) (SEQ ID NO:1468)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h23) (SEQ ID NO:1469)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h24) (SEQ ID NO:1470)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h25) (SEQ ID NO:1471)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h26) (SEQ ID NO:1472)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h27) (SEQ ID NO:1473)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h28) (SEQ ID NO:1474)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h29) (SEQ ID NO:1475)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h30) (SEQ ID NO:1476)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h31) (SEQ ID NO:1477)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h32) (SEQ ID NO:1478)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h33) (SEQ ID NO:1479)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h34) (SEQ ID NO:1480)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h35) (SEQ ID NO:1481)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h36) (SEQ ID NO:1482)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h37) (SEQ ID NO:1483)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h38) (SEQ ID NO:1484)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h39) (SEQ ID NO:1485)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h40) (SEQ ID NO:1486)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h41) (SEQ ID NO:1487)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h42) (SEQ ID NO:1488)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h43) (SEQ ID NO:1489)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h44) (SEQ ID NO:1490)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h45) (SEQ ID NO:1491)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h46) (SEQ ID NO:1492)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h47) (SEQ ID NO:1493)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h48) (SEQ ID NO:1494)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h49) (SEQ ID NO:1495)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h50) (SEQ ID NO:1496)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h51) (SEQ ID NO:1497)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h52) (SEQ ID NO:1498)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h53) (SEQ ID NO:1499)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h54) (SEQ ID NO:1500)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h55) (SEQ ID NO:1501)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h56) (SEQ ID NO:1502)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h57) (SEQ ID NO:1503)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂CCL28-(1-14)-[linker]-CCL28-(88-102) acid or amide h58) (SEQ ID NO:1504)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h59) (SEQ ID NO:1505)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h60) (SEQ ID NO:1506)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h61) (SEQ ID NO:1507)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h62) (SEQ ID NO:1508)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h63) (SEQ ID NO:1509)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h64) (SEQ ID NO:1510)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h65) (SEQ ID NO:1511)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h66) (SEQ ID NO:1512)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h67) (SEQ ID NO:1513)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h68) (SEQ ID NO:1514)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h69) (SEQ ID NO:1515)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h70) (SEQ ID NO:1516)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h71) (SEQ ID NO:1517)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h72) (SEQ ID NO:1518)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h73) (SEQ ID NO:1519)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h74) (SEQ ID NO:1520)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h75) (SEQ ID NO:1521)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h76) (SEQ ID NO:1522)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h77) (SEQ ID NO:1523)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h78) (SEQ ID NO:1524)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h79) (SEQ ID NO:1525)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h80) (SEQ ID NO:1526)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h81) (SEQ ID NO:1527)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h82) (SEQ ID NO:1528)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h83) (SEQ ID NO:1529)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h84) (SEQ ID NO:1530)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h85) (SEQ ID NO:1531)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h86) (SEQ ID NO:1532)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h87) (SEQ ID NO:1533)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h88) (SEQ ID NO:1534)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h89) (SEQ ID NO:1535)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h90) (SEQ ID NO:1536)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h91) (SEQ ID NO:1537)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h92) (SEQ ID NO:1538)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h93) (SEQ ID NO:1539)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h94) (SEQ ID NO:1540)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h95) (SEQ ID NO:1541)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h96) (SEQ ID NO:1542)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h97) (SEQ ID NO:1543)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h98) (SEQ ID NO:1544)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h99) (SEQ ID NO:1545)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂

Preferred embodiments of cyclic CCL28 analogs of the present inventioncorresponding to a portion the N-terminal region joined with a linker toa cyclic portion of the C-terminal region of CCL28 having the followingstructures: CCL28-(1-14)-[linker]-[Asp⁸⁶]-CCL28-(75-88)-cyclic(Lys82-Asp86) acid or amide h100) (SEQ ID NO:1546)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Ser-Cys-Cys-Thr-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h101) (SEQ ID NO:1547)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h102) (SEQ ID NO:1548)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h103) (SEQ ID NO:1549)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h104) (SEQ ID NO:1550)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h105) (SEQ ID NO:1551)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h106) (SEQ ID NO:1552)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h107) (SEQ ID NO:1553)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h108) (SEQ ID NO:1554)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h109) (SEQ ID NO:1555)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h110) (SEQ ID NO:1556)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h111) (SEQ ID NO:1557)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h112) (SEQ ID NO:1558)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h113) (SEQ ID NO:1559)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h114) (SEQ ID NO:1560)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h115) (SEQ ID NO:1561)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h116) (SEQ ID NO:1562)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h117) (SEQ ID NO:1563)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h118) (SEQ ID NO:1564)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h119) (SEQ ID NO:1565)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h120) (SEQ ID NO:1566)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h121) (SEQ ID NO:1567)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h122) (SEQ ID NO:1568)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h123) (SEQ ID NO:1569)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h124) (SEQ ID NO:1570)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h125) (SEQ ID NO:1571)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h125) (SEQ ID NO:1572)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h126) (SEQ ID NO:1573)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h127) (SEQ ID NO:1574)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h128) (SEQ ID NO:1575)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h129) (SEQ ID NO:1576)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h130) (SEQ ID NO:1577)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h131) (SEQ ID NO:1578)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h132) (SEQ ID NO:1579)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h133) (SEQ ID NO:1580)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h134) (SEQ ID NO:1581)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h135) (SEQ ID NO:1582)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h136) (SEQ ID NO:1583)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h137) (SEQ ID NO:1584)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h138) (SEQ ID NO:1585)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h139) (SEQ ID NO:1586)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h140) (SEQ ID NO:1587)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂ h141) (SEQ ID NO:1588)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-His-Arg-Lys-Lys-His-His-Gly-Lys-Arg-Asn-Ser-Asp-Arg-Ala-(OH)NH₂CCL28-(1-14)-[linker]-CCL28-(88-102)-cyclic(Glu94- Lys99) acid or amideh142) (SEQ ID NO:1589) RNH-Ile-Leu-Pro-Ile-Ala-Ser-Ser-Cys-Cys-Thr-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h143) (SEQ ID NO:1590)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h144) (SEQ ID NO:1591)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h145) (SEQ ID NO:1592)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h146) (SEQ ID NO:1593)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h147) (SEQ ID NO:1594)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h148) (SEQ ID NO:1595)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h149) (SEQ ID NO:1596)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h150) (SEQ ID NO:1597)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h151) (SEQ ID NO:1598)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h152) (SEQ ID NO:1599)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h153) (SEQ ID NO:1600)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h154) (SEQ ID NO:1601)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h155) (SEQ ID NO:1602)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h156) (SEQ ID NO:1603)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Xaa₄-Glu-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h157) (SEQ ID NO:1604)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h158) (SEQ ID NO:1605)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h159) (SEQ ID NO:1606)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h160) (SEQ ID NO:1607)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h161) (SEQ ID NO:1608)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h162) (SEQ ID NO:1609)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h163) (SEQ ID NO:1610)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Xaa₄-Val-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h164) (SEQ ID NO:1611)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h165) (SEQ ID NO:1612)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h166) (SEQ ID NO:1613)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h167) (SEQ ID NO:1614)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h168) (SEQ ID NO:1615)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h169) (SEQ ID NO:1616)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h170) (SEQ ID NO:1617)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Glu-Xaa₄-Ser-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h171) (SEQ ID NO:1618)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h172) (SEQ ID NO:1619)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h173) (SEQ ID NO:1620)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h174) (SEQ ID NO:1621)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h175) (SEQ ID NO:1622)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h176) (SEQ ID NO:1623)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h177) (SEQ ID NO:1624)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Glu-Val-Xaa₄-His-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h178) (SEQ ID NO:1625)RNH-Xaa₃-Leu-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h179) (SEQ ID NO:1626)RNH-Ile-Xaa₃-Pro-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h180) (SEQ ID NO:1627)RNH-Ile-Leu-Xaa₃-Ile-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h181) (SEQ ID NO:1628)RNH-Ile-Leu-Pro-Xaa₃-Ala-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h182) (SEQ ID NO:1629)RNH-Ile-Leu-Pro-Ile-Xaa₃-Ser-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h183) (SEQ ID NO:1630)RNH-Ile-Leu-Pro-Ile-Ala-Xaa₃-Ser-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂ h184) (SEQ ID NO:1631)RNH-Ile-Leu-Pro-Ile-Ala-Ser-Xaa₃-Xaa₁-Xaa₂-Thr-Glu-Val-Ser-Xaa₄-[linker]-Ala-His-Gln-Gly-Lys-His-Glu-Thr-Tyr-Gly-His-Lys-Thr-Pro-Tyr-(OH)NH₂

In the above structures:

-   R is selected from the group consisting of hydrogen, alkyl, alkenyl,    alkynyl, alkylcarbonyl, arylcarbonyl, aryl, PEG (polyethyleneglycol)    and any other modifying group.-   Xaa₃ is selected from the group consisting of L-Pro, D-Pro, P* , Btd    and any L- or D-natural and non-natural amino acid.-   Xaa₄ is selected from the group consisting of P* , Btd and any L- or    D-natural amino acid and any non-natural amino acid.    -   P* is:        with Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl,        arylcarbonyl, aryl, aryl-hydroxy, and more

A wide variety of amino acid substitutions may be made in polypeptidesequences, such as lysine to glutamic acid, lysine to aspartic acid, Ornto Glu, or Orn to Asp. Moieties other than naturally occurring aminoacids may also be substituted, such as Btd:

-   -   Btd* is:    -   Z=hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl,        arylcarbonyl, aryl, aryl-hydroxy, and more

-   Xaa₁ is selected from the group consisting of any L- or D-natural    amino acid and any non-natural amino acid.

-   Xaa₂ is selected from the group consisting of any L- or D-natural    amino acid and any non-natural amino acid.

The linker is a bifunctional group covalently attached to the N-terminaland C-terminal portions of the analog having the structure:H₂N—Z_(A)—COOH wherein Z_(A) is selected from the group consisting of:(1) alkyl, alkenyl, aralkyl, and alkynyl; (2) —(CH₂)_(n)— wherein n isan integer, n=9 to 14; (3) any combination of four natural amino acidsor non-natural amino acids; and (4) —(gly)₄—.

Compositions

The invention further provides pharmaceutical compositions containingchemokine receptor agonists or antagonists. In one embodiment, suchcompositions include a chemokine analog compound in a therapeutically,diagnostically or prophylactically effective amount sufficient to beused in treating diseases or disorders selected from the groupconsisting of autoimmune diseases, acute chronic inflammation, cancer,cardiovascular disease, infectious disease, and inflammatory disordersincluding rheumatoid arthritis, chronic inflammatory bowel disease,chronic inflammatory pelvic disease, multiple sclerosis, asthma,osteoarthritis, atherosclerosis, psoriasis, rhinitis, autoimmunity, andorgan transplant rejection. In another embodiment, such compositionsinclude a chemokine analog compound in a therapeutically orprophylactically effective amount sufficient to be used to increase thehemocrit, assist in mobilizing and recovering stem cells, stimulate theproduction of blood cells, assist in vaccine production, or assist ingene therapy.

An “effective amount” of a compound of the invention includes atherapeutically effective amount or a prophylatically effective amount.A “therapeutically effective amount” refers to an amount effective, atdosages and for periods of time necessary, to achieve the desiredtherapeutic result. The term “therapeutically effective amount” may alsorefer to that amount of active compound, prodrug or pharmaceutical agentthat elicits a biological or medicinal response in a tissue, system,animal or human that is being sought by a researcher, veterinarian,medical doctor or other clinician in order to provide a therapeuticeffect.

A “prophylactically effective amount” refers to an amount effective, atdosages and for periods of time necessary, to achieve the desiredprophylactic result, such as preventing or inhibiting a cytotoxic effectof a cytotoxic agent. Typically, a prophylactic dose is used inorganisms prior to or at an earlier stage of disease, so that aprophylactically effective amount may be less than a therapeuticallyeffective amount. The term “preventing” refers to decreasing theprobability that an organism contracts or develops an abnormalcondition.

In particular embodiments, a preferred range for therapeutically orprophylactically effective amounts of chemokine analogs may be 0.1nM-0.1 M, 0.1 nM-0.05 M, 0.05 nM-15 μM or 0.01 nM-10 μM. It is to benoted that dosage values may vary with the severity of the condition tobe alleviated. For any particular subject, specific dosage regimens maybe adjusted over time according to the individual need and theprofessional judgement of the person administering or supervising theadministration of the compositions. Dosage ranges set forth herein areexemplary only and do not limit the dosage ranges that may be selectedby medical practitioners.

The amount of active compound in the composition may vary according tofactors such as the disease state, age, sex, and weight of theindividual. Dosage regimens may be adjusted to provide the optimumtherapeutic response. For example, a single bolus may be administered,several divided doses may be administered over time or the dose may beproportionally reduced or increased as indicated by the exigencies ofthe therapeutic situation. It may be advantageous to formulateparenteral compositions in dosage unit form for ease of administrationand uniformity of dosage. “Dosage unit form” as used herein refers tophysically discrete units suited as unitary dosages for subjects to betreated; each unit containing a predetermined quantity of activecompound calculated to produce the desired therapeutic effect inassociation with the required pharmaceutical carrier. The specificationfor the dosage unit forms of the invention are dictated by and directlydependent on (a) the unique characteristics of the active compound andthe particular therapeutic effect to be achieved, and (b) thelimitations inherent in the art of compounding such an active compoundfor the treatment of sensitivity in individuals.

The terms “administration” or “administering” refer to a method ofincorporating a compound into the cells or tissues of an animal,preferably a mammal, and still more preferably a human, in order totreat or prevent an abnormal condition. When the compound or prodrug ofthe invention is provided in combination with one or active agents, theterms “administration” or “administering” include sequential orconcurrent introduction of the compound or prodrug with the otheragent(s). For cells harbored within the organism, many techniques existin the art to administer compounds, including (but not limited to) oral,injection, parenteral, dermal, and aerosol applications.

The term “therapeutic effect” refers to the inhibition or activation offactors causing or contributing to the abnormal condition (including adisease or disorder). A therapeutic effect relieves or prevents to someextent one or more of the symptoms of the abnormal condition. Inreference to the treatment of abnormal conditions, a therapeutic effectcan refer to one or more of the following: (a) an increase or decreasein the number of lymphocytic cells present at a specified location, (b)an increase or decrease in the ability of lymphocytic cells to migrate,(c) an increase or decrease in the response of lymphocytic cells to astimulus, (d) an increase or decrease in the proliferation, growth,and/or differentiation of cells; (e) inhibition (i.e., slowing orstopping) or acceleration of cell death; (f) relieving, to some extent,one or more of the symptoms associated with an abnormal condition; (g)enhancing or inhibiting the function of the affected population ofcells; (h) activating an enzyme activity present in cells associatedwith the abnormal condition; and (i) inhibiting an enzyme activitypresent in cells associated with the abnormal condition.

The term “abnormal condition” refers to a function in the cells ortissues of an organism that deviates from their normal functions in thatorganism and includes, but is not limited to, conditions commonlyreferred to as diseases or disorders. An abnormal condition can relateto cell proliferation, cell differentiation, cell survival, cellmigration or movement, or the activities of enzymes within a cell.Diseases and disorders may include inflammatory disorders includingrheumatoid arthritis, chronic inflammatory bowel disease, chronicinflammatory pelvic disease, multiple sclerosis, asthma, osteoarthritis,atherosclerosis, psoriasis, rhinitis, autoimmunity, organ transplantrejection, and genetic diseases.

As used herein “pharmaceutically acceptable carrier” or “excipient”includes any and all solvents, dispersion media, coatings, antibacterialand antifungal agents, isotonic and absorption delaying agents, and thelike that are physiologically compatible. In one embodiment, the carrieris suitable for parenteral administration. Alternatively, the carriercan be suitable for intravenous, intraperitoneal, intramuscular,sublingual or oral administration. Pharmaceutically acceptable carriersinclude sterile aqueous solutions or dispersions and sterile powders forthe extemporaneous preparation of sterile injectable solutions ordispersion. The use of such media and agents for pharmaceutically activesubstances is well known in the art. Except insofar as any conventionalmedia or agent is incompatible with the active compound, use thereof inthe pharmaceutical compositions of the invention is contemplated.Supplementary active compounds can also be incorporated into thecompositions. Pharmaceutically acceptable carrier “may comprisepharmaceutically acceptable salts.”

Pharmaceutical formulations for parenteral administration may includeliposomes. Liposomes and emulsions are well known examples of deliveryvehicles or carriers that are especially useful for hydrophobic drugs.Depending on biological stability of the therapeutic reagent, additionalstrategies for protein stabilization may be employed. Furthermore, onemay administer the drug in a targeted drug delivery system, for example,in a liposome coated with target-specific antibody. The liposomes willbind to the target protein and be taken up selectively by the cellexpressing the target protein.

Therapeutic compositions typically must be sterile and stable under theconditions of manufacture and storage. The composition can be formulatedas a solution, microemulsion, liposome, or other ordered structuresuitable to high drug concentration. The carrier can be a solvent ordispersion medium containing, for example, water, ethanol, polyol (forexample, glycerol, propylene glycol, and liquid polyethylene glycol, andthe like), and suitable mixtures thereof. The proper fluidity can bemaintained, for example, by the use of a coating such as lecithin, bythe maintenance of the required particle size in the case of dispersionand by the use of surfactants. In many cases, it will be preferable toinclude isotonic agents, for example, sugars, polyalcohols such asmannitol, sorbitol, or sodium chloride in the composition. Prolongedabsorption of the injectable compositions can be brought about byincluding in the composition an agent which delays absorption, forexample, monostearate salts and gelatin. Moreover, the chemokine analogsmay be administered in a time release formulation, for example in acomposition which includes a slow release polymer. The active compoundscan be prepared with carriers that will protect the compound againstrapid release, such as a controlled release formulation, includingimplants and microencapsulated delivery systems. Biodegradable,biocompatible polymers can be used, such as ethylene vinyl acetate,polyanihydrides, polyglycolic acid, collagen, polyorthoesters,polylactic acid and polylactic, polyglycolic copolymers (PLG). Manymethods for the preparation of such formulations are patented orgenerally known to those skilled in the art.

Additionally, suspensions of the compounds of the invention may beprepared as appropriate oily suspensions for injection. Suitablelipophilic solvents or vehicles include fatty oils such as sesame oil;or synthetic fatty acid esters, such as ethyl oleate or triglycerides;or liposomes. Suspensions to be used for injection may also containsubstances which increase the viscosity of the suspension, such assodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, thesuspension may also contain suitable stabilizers or agents whichincrease the solubility of the compounds to allow for the preparation ofhighly concentrated solutions.

Sterile injectable solutions can be prepared by incorporating the activecompound in the required amount in an appropriate solvent with one or acombination of ingredients enumerated above, as required, followed byfiltered sterilization. Generally, dispersions are prepared byincorporating the active compound into a sterile vehicle that contains abasic dispersion medium and the required other ingredients from thoseenumerated above. In the case of sterile powders for the preparation ofsterile injectable solutions, the preferred methods of preparation arevacuum drying and freeze-drying which yields a powder of the activeingredient plus any additional desired ingredient from a previouslysterile-filtered solution thereof. In accordance with an alternativeaspect of the invention, a chemokine analog may be formulated with oneor more additional compounds that enhance the solubility of thechemokine analog.

If the compounds of the invention are to be administered by inhalation,they may be conveniently delivered in the form of an aerosol spraypresentation from pressurized packs or a nebuliser, together with theuse of a suitable propellant, e.g., dichlorodifluoromethane,trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide orother suitable gas. In the case of a pressurized aerosol the dosage unitmay be determined by providing a valve to deliver a metered amount.Capsules and cartridges of gelatin, for example, for use in an inhalermay be formulated containing a powder mix of the compound and a suitablepowder base such as starch or lactose.

The term “modulates” refers to altering the function or activity of achemokine receptor by contacting it with a chemokine or chemokine analogand thus increasing or decreasing the probability that a complex formsbetween the receptor and a natural binding partner. A chemokine orchemokine analog preferably increases the probability that such acomplex forms between the chemokine receptor and the natural bindingpartner, more preferably increases or decreases the probability that acomplex forms between the chemokine receptor and the natural bindingpartner depending on the concentration of the chemokine or chemokineanalog exposed to the receptor, and most preferably decreases theprobability that a complex forms between the chemokine receptor and thenatural binding partner depending on the concentration of the chemokineor chemokine analog exposed to the polypeptide.

The term “chemokine receptor” refers to a chemokine receptor as the termis used by one skilled in the art and also refers to any otherpolypeptide capable of binding a chemokine or chemokine analog.

In preferred embodiments, a modulator preferably activates the catalyticactivity of a chemokine receptor, more preferably activates or inhibitsthe catalytic activity of a chemokine receptor depending on theconcentration of the chemokine or chemokine analog exposed to thechemokine receptor, or most preferably inhibits the catalytic activityof a chemokine receptor depending on the concentration of the chemokineor chemokine analog exposed to the chemokine receptor.

The term “natural binding partner” refers to G proteins, polypeptides,lipids, small molecules, or nucleic acids that bind to chemokinereceptors in cells or in the extracellular environment. The term naturalbinding partner includes a substrate to be acted upon by the chemokinereceptor. A change in the interaction between a chemokine receptor and anatural binding partner can manifest itself as an increased or decreasedprobability that the interaction forms, or an increased or decreasedconcentration of chemokine receptor/natural binding partner complex.This can result in a decreased or increased activity of the chemokinereceptor.

The terms “activated,” “activating,” and “activation” refer to anincrease in the cellular or extracellular function of a chemokinereceptor. The chemokine receptor function is preferably the interactionwith a natural binding partner, and most preferably catalytic activity.The term “inhibits” refers to decreasing the cellular or extracellularactivity of the chemokine receptor. The cellular or extracellularactivity of a chemokine receptor is preferably the interaction with anatural binding partner, and most preferably catalytic activity.

The term “complex” refers to an assembly of at least two molecules boundto one another. A signal transduction complex often contains at leasttwo protein molecules bound to one another. For instance, a proteintyrosine receptor protein kinase, GRB2, SOS, RAF, and RAS assemble toform a signal transduction complex in response to a mitogenic ligand.Another example is a chemokine bound to a chemokine receptor. Stillanother example is a G protein bound to a chemokine receptor.

The term “contacting” as used herein refers to adding together asolution or a composition comprising the chemokine or chemokine analogwith a liquid medium bathing the polypeptide or cells comprising achemokine receptor. The solution comprising the chemokine or chemokineanalog may also comprise another component, such as dimethyl sulfoxide(DMSO), which facilitates the uptake of the chemokine or chemokineanalog into the cells of the methods. The solution comprising thechemokine or chemokine analog may be added to the medium bathing thecells by utilizing a delivery apparatus, such as a pipette-based deviceor syringe-based device.

As discussed supra, compounds of the present invention may prove usefulin increasing the hemocrit, mobilizing stem cells, or in assisting invaccine production or otherwise stimulating the immune system toeffectuate tumor destruction. For example, the chemokine SDF-1 has beenshown to enhance platelet production (Lane et al., Blood 96:4152-59,2000) and B-cell production (Nagasawa, T., Int. J. Hematol. 72:408-11,2000), inter alia. Analogs of chemokines may also be useful in improvingthe engraftment of stem cells following transplantation (Nagasawa,2000). Chemokine analogs of the invention may also prove useful inmobilizing stem cells (Gazitt, Y., J. Hematother Stem Cell Res10:229-36, 2001; Hattori et al., Blood 97:3354-59, 2001). They may alsoprove useful in enhancing anti-tumor immunity (Nomura et al., Int. J.Cancer 91:597-606, 2001; Mach and Dranoff, Curr. Opin. Immunol.12:571-75, 2000). Other aspects and roles of modulating chemokinefunction are reviewed in Schwarz and Wells (Schwarz and Wells, Nat. Rev.Drug Discov. 1:347-58, 2002). Chemokine analogs of the present inventionmay also prove useful in facilitating gene therapy. Glimm and colleaguesreported that one chemokine, SDF-1, arrests hematopoietic stem cellcycling, thus allowing a better transfection of these cells with geneconstructs for the purpose of gene therapy (Glimm H. et al., “Ex vivotreatment of proliferating human cord blood stem cells withstroma-derived factor-1 enhances their ability to engraft NOD/SCIDmice,” Blood 99(9):3454-57, 2002). All of the above references areincorporated by reference herein their entirety, including any drawings,tables, and figures.

EXAMPLES

The following examples illustrate, but do not limit, the presentinvention.

Example 1

The efficacy of chemokine analogs of the invention as chemokine receptoragonists is demonstrated through receptor binding assays. A competitivedose response for binding to a chemokine receptor by the natural bindingchemokine, another chemokine, and chemokine analogs of the invention maybe demonstrated by the method set forth in Daugherty et al., Methods inMolecular Biology v138 “Chemokine Protocols” edited by Proudfoot et al.,Human Press, Totowa, N.J. p129-148, 2000, which is hereby incorporatedby reference in its entirety, including any figures, tables anddrawings.

Example 2

The efficacy of chemokine analogs of the invention as chemokine receptoragonists is demonstrated through chemotaxis assays. The effect of anative chemokine and chemokine analogs of the invention may be comparedby the method set forth in Ponath et al., Methods in Molecular Biologyv138 “Chemokine Protocols” edited by Proudfoot et al., Human Press,Totowa, N.J. p113-120, 2000, which is hereby incorporated by referencein its entirety, including any figures, tables and drawings.

Example 3

(IL-8)

The efficacy of IL-8 and IL-8 peptide analogs as CXCR1 and CXCP2agonists was demonstrated through CXCR1 and CXCR2 receptor bindingassays. A competitive dose response for binding to the IL-8 receptor bynative IL-8 and the CXCR1 and CXCR2 agonists against ¹²⁵I-IL-8 is shownin FIG. 1. THP-1 cells, a human monocytoid cell line, were preincubatedwith the IL-8 or IL-8 analogs for 30 min, then were assessed for¹²⁵I-IL-8 binding following 2 hr of incubation with ¹²⁵I-IL-8. 10nM¹²⁵I-IL-8 was added in the presence of IL-8 and the indicated analogs(competing ligands) at the concentrations illustrated. The results areexpressed as percentages of the maximal specific binding that wasdetermined without competing ligand. A concentration-dependentinhibition of ¹²⁵I-IL-8 is illustrated, indicating the affinity of IL-8for the receptor. The inhibition of ¹²⁵I-IL-8 by IL-8 and the IL-8analogs is indicative of CXCR1 and CXCR2 receptor binding. The compoundsillustrated in the figure are as follows: IL-8, Compounds A, B, and C.Compound A (SEQ ID NO:1632)H₂N-Ser-Ala-Lys-Glu-Leu-Arg-Cys-Gln-Cys-Ile-Lys-Thr-Tyr-Ser-Lys-[Gly-Gly-Gly-Gly]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂. Compound B(SEQ ID NO:1633) H₂N-Ser-Ala-Lys-Glu-Leu-Arg-Cys-Gln-Cys-Ile-Lys-Thr-Tyr-[Gly-Gly-Gly-Gly]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂. Compound C (SEQ IDNO:1634) H₂N-Ser-Ala-Lys-Glu-Leu-Arg-Cys-Gln-Cys-Ile-Lys-[Gly-Gly-Gly-Gly]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂.

Example 4

(I-309)

This example illustrates the efficacy of I-309 peptide analogs inmediating intracellular calcium mobilization ([Ca²+]_(i)). To illustratethat the binding of I-309 peptide analogs results in the agonisticactivation of the CCR8 receptor, [Ca²+]_(i) mobilization assays wereconducted, the results of which are shown in FIG. 2. To obtain the datashown in FIG. 2, Fluo-4,AM loaded human peripheral blood mononuclearcells (PBMC), at 5×10⁶ cells/ml, were stimulated with Compounds D, E, F,G and H at the concentrations indicated. The values represent themean+/−one S.D. As shown by the data in FIG. 2, incubation of PBMC withCompounds E, F and G resulted in the receptor-mediated induction of[Ca²+]_(i) mobilization. Compound D: (SEQ ID NO:1635)H₂N-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Ala-NH₂. Compound E: (SEQ IDNO:1636) H₂N-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala-Ile-Leu-NH₂. Compound F: (SEQ ID NO:1637)H₂N-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala-Ile-Leu-Cys-Tyr-Arg-Asn-Thr-Ser-Ser-Ile- NH₂. Compound G: (SEQID NO:1638) H₂N-Ala-Tyr-Arg-Asn-Thr-Ser-Ser-Ile-Cys-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu- Ala-NH₂. Compound H:(SEQ ID NO:1639) H₂N-Ala-Ala-Leu-Asp-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-His-Cys-Pro-Ser-Lys-Arg- Lys-(OH)NH₂.

Example 5

Peptides of the invention may be synthesized chemically using theFmoc/tBu strategy on a continuous flow peptide synthesizer, as forexample has been carried out using the following protocols:

Reagents (solvents, support, chemicals)

Main Solvent: N,N-Dimethylformamide (DMF): certified ACS spectroanalyzedfrom Fisher (D131-4) M. W=73.10. The DMF is treated with activatedmolecular sieves, type 4A (from BDH: B54005) for at least two weeks thentested with FDNB (2,4-Dinitrofluorobenzene from Eastman).

Procedure: Mix equal volumes of FDNB solution (1 mg/ml in 95% EtOH) andDMF; Let stand 30 minutes; read the absorbance at 381 nm over a FDNBblank (0.5 ml FDNB+0.5 ml 95% EtOH). If the absorbance˜0.2, the DMF issuitable to be used for the synthesis.

Deblocking Agent: 20% Piperidine (from Aldrich Chemical company, catalogNo: 10,409-4) in DMF containing 0.5 % Triton X100 v/v ( from Sigma,catalg No: T-9284).

Activating Agents: 2-(H-benzotriazol-1 yl) 1,1,3,3-tetramethyluroniumtetrafluoroborate (TBTU: M. W.=321.09. from Quantum Richilieu, catalogNo: R0139)/Hydroxybenzotriazole (HOBt M. W.=135.1 from QuantumRichilieu, catalog No.: R0166-100) respectively, 0.52 M in DMF and4-Methylmorpholine (NMM; M. W.=101.15, d=0.926 from Aldrich, catalogNo.: M5,655-7): 0.9 M in DMF or in the case of sensitive amino acids toracemization like Cys, we use 2,4,6-Collidine, 99% ( M. W.=121.18,d=0.917, from Aldrich, catalog No: 14,238-7): 0.78M in DMF/DCM, 1/1 v/v.

Support: TentaGel R RAM (90 μm), RinK-type Fmoc (from PeptidesInternational, catalog No.: RTS -9995-PI): 0.21 mmol/g, 0.5 g for 0.1mmol of peptide.

Fmoc-L-amino derivative, side-chains protected with: Boc; tBu; Trtgroups: with 4 fold excess (from Peptides International, Bachem,Novabiochem, Chem-Impex Inc). Glu24 and Lys24 are Allyl-protected (fromMillipore/Perseptive Biosystems).

Initial Amino Loading and Peptide Synthesis Procedure

The first amino acid Asn31 and the remaining residues are double coupledat room temp. or at 45° C. automatically with 4-fold excess in eachcoupling. The synthesis is interrupted after residue Leu19. Thepeptide-bound support is removed from the synthesizer column and placedin a react-vial containing a small magnetic bar for gentle stirring.

Removal of The Allyl Groups

A solution of tetrakis(triphenylphosphine)Palladium(0) Pd(PPh3)4 (fromSigma-Aldrich, catalog No: 21,666-6); M. W.=1155.58×0.1 mmol peptide×3fold=347 mg dissolved in 5% Acetic Acid; 2.5% NMM in CHC13 to 0.14 M,under argon. The solution is added to the support-bound peptidepreviously removed from the coulmn in a reactvial containing a smallmangnetic bar for gentle stirring. The mixture is flushed with argon,sealed and stirred at room temperature for 6 hours. The support-boundpeptide is transferred to a filter funnel, washed with 30 ml of asolution made of 0.5% Sodium Diethyldithiocarbonate/in DMF, then DCM;DCM/DMF (1:1) and DMF. A positive Kaiser test indicate the deprotectionof the amino side. chaine of the Lys20.

Lactam Formation:

Activating agent: 7-Azabenztriazol-1-yloxytris (pyrrolindino)phosphonium-hexafluorophosphate (PyAOP: M. W.=521.7 from PerSeptiveBiosystems GmbH, catalog No: GEN076531), 1.4-fold: 0.105mmol×1.4×521.7=76.6 mg and NMM 1.5-fold: 0.105×1.4×1.5=0.23 mmolv=0.23/0.9 M NMM solution=263 μl).

The cyclisation may be carried out in an amino acid vial at roomtemperature overnight (˜16 hours) with gentle agitation. The completionof cyclization may be indicated by a negative kaiser test. Thesupport-bound peptide may be poured into the column, washed with DMF andthe synthesis continues to completion, with a cyclic amide bridgethereby introduced into the peptide.

Final Product Removal From The Support:

The support-bound peptide is removed from the synthesizer in to a mediumfilter funnel, washed with DCM to replace the non-volatile DMF andthoroughly dried under high vacuum for at least two hours, orpreferably, overnight.

Cleavage Mixture (Reagent K):

-   TFA/Phenol/Water/Thio-Anisol/EDT (82/5/5/5/2.5); 7.5 ml

Support: 0.5 g resin-peptide. TFA 6.15 ml (Biograde from Halocarbon)Phenol 0.375 ml (Aldrich) Water 0.375 ml (MillQ) Thio-Anisol 0.375 ml(Aldrich) EDT 0.187 ml (Aldrich) Total 7.5 ml

The cleavage may be performed at room temperature for 4 hours withgentle agitation on a rocker.

Precipitation of the Peptide

The cleaved peptide solution is filtered through a filter funnel in a 50ml round bottom flask. The support is rinsed twice with 4 ml TFA. TheTFA solution is concentrated on a rotavap and added drop wise into acold diethyl ether previously treated with activated neutral aluminumoxide to make it free of peroxide. Approximately 10-fold excess of etherare used. The beads are stored until the yield is determined and peptidecharacterized. The precipitate is collected at room temperature in screwcapped 50 ml polypropylene vial by centrifugation at 2K rpm using a topbench centrifuge (4 minutes run time). The pellet is washed 3×with coldether, centrifuged and dried with a flow of argon. The precipitate isdissolved in 20% acetonitrile, 0.1% TFA and lyophilized.

Crude Product Characterization:

The product is characterized by analytical HPLC.

-   Experimental conditions: Column: Vydac 218TP54: C18 reversed-phase 5    μm, 4.6 mm ID×150 mm L.-   Eluants: 0.1% TFA/H₂O (solvant A); 0.1% TFA/acetonitrile (solvent    B).-   Elution Conditions: 20-50% B (40 min); 60-90% B (5 min); 90-20% B (5    min); 20% B (10 min). At 1.0 ml/min and A214 nm=0.5 absorbance unit    full scale.    Sample Preparation:

An aliquot of the product is weighed and dissolved in 20% acetonitrile0.1% TFA at a concentration of 2 mg/ml. The solution is microfuged and20μl is applied onto the column. The main peak or the major peaks arecollected, SpeedVac dried and molecular weight determined by massspectrometry.

Structure of some of the compounds used in this study is shown below.

Compound A or a19 (SEQ ID NO:27), wherein R═H, Xaa₁=Cys, Xaa₂=Cys,[linker]=4* Gly): (SEQ ID NO:1632)H₂N-Ser-Ala-Lys-Glu-Leu-Arg-Cys-Gln-Cys-Ile-Lys-Thr-Tyr-Ser-Lys-[Gly-Gly-Gly-Gly]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn- (OH)NH₂.

Compound B or a49 (SEQ ID NO:56), wherein R═H, Xaa₁=Cys, Xaa₂=Cys,[linker]=4* Gly): (SEQ ID NO:1633)H₂N-Ser-Ala-Lys-Glu-Leu-Arg-Cys-Gln-Cys-Ile-Lys-Thr-Tyr-[Gly-Gly-Gly-Gly]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂.

Compound C or a70 (SEQ ID NO:77), wherein R═H, Xaa₁=Cys, Xaa₂=Cys,[linker]=4* Gly): (SEQ ID NO:1634)H₂N-Ser-Ala-Lys-Glu-Leu-Arg-Cys-Gln-Cys-Ile-Lys-[Gly-Gly-Gly-Gly]-Asn-Trp-Val-Gln-Arg-Val-Val-Glu-Lys-Phe-Leu-Lys-Arg-Ala-Glu-Asn-(OH)NH₂.

Compound D or el (SEQ ID NO:972), wherein R═H): (SEQ ID NO:1635)H₂N-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Ala-NH₂.

Compound E or e2 (SEQ ID NO:973), wherein R═H) (SEQ ID NO:1636)H₂N-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu- Arg-Ala-Ile-Leu-NH₂.

Compound F or e3 (SEQ ID NO:974), wherein R═H): (SEQ ID NO:1637)H₂N-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala-Ile-Leu-Cys-Tyr-Arg-Asn-Thr-Ser-Ser-Ile- NH₂.

Compound G or e4 (SEQ ID NO:975), wherein R═H): (SEQ ID NO:1638)H₂N-Ala-Tyr-Arg-Asn-Thr-Ser-Ser-Ile-Cys-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu- Ala-NH₂.

Compound H or e17 (SEQ ID NO:988), wherein R═H): (SEQ ID NO:1639)H₂N-Ala-Ala-Leu-Asp-Thr-Val-Gly-Trp-Val-Gln-Arg-His-Arg-Lys-Met-Leu-Arg-His-Cys-Pro-Ser-Lys-Arg- Lys-(OH)NH₂.

The invention illustratively described herein can suitably be practicedin the absence of any element or elements, limitation or limitationsthat is not specifically disclosed herein. Thus, for example, the terms“comprising,” “including,” “containing,” etc., shall be read expansivelyand without limitation. Additionally, the terms and expressions employedherein have been used as terms of description and not of limitation, andthere is no intention in the use of such terms and expressions ofexcluding any equivalent of the invention shown or portion thereof, butit is recognized that various modifications are possible within thescope of the invention claimed. Thus, it should be understood thatalthough the present invention has been specifically disclosed bypreferred embodiments and optional features, modifications andvariations of the inventions embodied herein disclosed can be readilymade by those skilled in the art, and that such modifications andvariations are considered to be within the scope of the inventionsdisclosed herein. The inventions have been described broadly andgenerically herein. Each of the narrower species and subgenericgroupings falling within the generic disclosure also form the part ofthese inventions. This includes within the generic description of eachof the inventions a proviso or negative limitation that will allowremoving any subject matter from the genus, regardless or whether or notthe material to be removed was specifically recited. In addition, wherefeatures or aspects of an invention are described in terms of theMarkush group, those schooled in the art will recognize that theinvention is also thereby described in terms of any individual member orsubgroup of members of the Markush group. Further, when a reference toan aspect of the invention lists a range of individual members, as forexample, ‘SEQ ID NO:9 to SEQ ID NO:162, inclusive,’ it is intended to beequivalent to listing every member of the list individually, andadditionally it should be understood that every individual member may beexcluded or included in the claim individually.

The steps depicted and/or used in methods herein may be performed in adifferent order than as depicted and/or stated. The steps are merelyexemplary of the order these steps may occur. The steps may occur in anyorder that is desired such that it still performs the goals of theclaimed invention.

From the description of the invention herein, it is manifest thatvarious equivalents can be used to implement the concepts of the presentinvention without departing from its scope. Moreover, while theinvention has been described with specific reference to certainembodiments, a person of ordinary skill in the art would recognize thatchanges can be made in form and detail without departing from the spiritand the scope of the invention. The described embodiments are consideredin all respects as illustrative and not restrictive. It should also beunderstood that the invention is not limited to the particularembodiments described herein, but is capable of many equivalents,rearrangements, modifications, and substitutions without departing fromthe scope of the invention. Thus, additional embodiments are within thescope of the invention and within the following claims.

Further, all patents and publications described herein are herebyincorporated by reference to the same extent as if each individualpatent or publication was specifically and individually indicated to beincorporated by reference.

1.-11. (canceled)
 12. An I-309 mimetic comprising an N-terminal regionand a C-terminal region, wherein the I-309 mimetic has a total of about10 to about 34 amino acid residues, and the N-terminal region comprisesa conserved amino acid sequence selected from a group consisting of SEQID NO:972, variant, e1, and conservative amino acid substitutionsthereof, and has the following general structure: (SEQ ID NO:972)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Ala- (OH)NH₂;

wherein, R is an N-terminal modifier comprising a component selectedfrom a group consisting of a hydrogen, a poly(ethylene glycol) orderivative thereof, a diagnostic label, an acyl group, an acetyl group,and a modifier capable of reducing the ability of the I-309 mimetic toact as a substrate for aminopeptidases; and, the (OH)NH₂ is a hydroxy oramine group that comprises the C-terminal region or attaches to anycombination of up to 7 additional amino acid residues that attach to alinker that attaches to the C-terminal region, wherein the C-terminalregion consists of amino acid residues 52-64 of SEQ ID NO:5; and, thelinker is (1) H₂N—Z_(A)—COOH, wherein Z_(A) is selected from the groupconsisting of saturated and unsaturated aliphatics consisting of 20 orfewer carbon atoms that are optionally substituted with a hydroxyl,carboxyl, carbonyl, thiol, amino, amido, imino, or aromatic group havingfrom 5 to 7 members in the ring; and —(CH₂)_(n)—, wherein n is aninteger ranging from 9 to 14; or (2) any combination of four naturalamino acids.
 13. The compound of claim 12, wherein the linker is11-aminoundecanoic acid.
 14. The composition of claim 12, wherein Rcomprises a poly(ethylene glycol), a glycosaminoglycan, or derivativethereof, each having a molecular weight of less than about 20,000Daltons.
 15. The composition of claim 12, wherein the conserved aminoacid sequence is selected from a group consisting of SEQ ID NO:1635 andconservative amino acid substitutions thereof, and has the followinggeneral structure: (SEQ ID NO:1635)H₂N-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Ala-NH₂.


16. The composition of claim 12, wherein the conserved amino acidsequence composes the first 10 amino acid residues of the I-309 mimetic.17. The composition of claim 12, wherein the C-terminal region iscyclized at Glu⁵⁷ and Lys⁶¹.
 18. The composition of claim 12, whereinthe I-309 mimetic is selected from a group consisting of SEQ ID NO:972,variant e1, and conservative amino acid substitutions thereof, and hasthe following general structure: (SEQ ID NO:972)RNH-Lys-Ser-Met-Gln-Val-Pro-Phe-Ser-Arg-Ala- (OH)NH₂;


19. An I-309 mimetic comprising an N-terminal region and a C-terminalregion, wherein the I-309 mimetic has a total of about 15 to about 25amino acid residues, and the N-terminal region or C-terminal regioncomprises a conserved amino acid sequence selected from a groupconsisting of SEQ ID NO:973, variant e2, and conservative amino acidsubstitutions thereof, and has the following general structure: (SEQ IDNO:973) RNH-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala-Ile-Leu-(OH)NH₂;

wherein, R is an N-terminal region or an N-terminal modifier comprisinga component selected from a group consisting of a hydrogen, apoly(ethylene glycol) or derivative thereof, a diagnostic label, an acylgroup, an acetyl group, and a modifier capable of reducing the abilityof the I-309 mimetic to act as a substrate for aminopeptidases; and, the(OH)NH₂ is a hydroxy or amine group that comprises the C-terminalregion, or attaches to any combination of additional amino acid residuescomposing the C-terminal region; and, the I-309 mimetic consistsessentially of the conserved amino acid sequence and from 0 to 10additional amino acid residues of any combination.
 20. The compositionof claim 19, wherein R comprises a poly(ethylene glycol), aglycosaminoglycan, or derivative thereof, each having a molecular weightof less than about 20,000 Daltons.
 21. The composition of claim 19,wherein the conserved amino acid sequence is selected from a groupconsisting of SEQ ID NO:1636 and conservative amino acid substitutionsthereof, and has the following general structure: (SEQ ID NO:1636)H₂N-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu- Arg-Ala-Ile-Leu-NH₂.


22. The composition of claim 19, wherein the conserved amino acidsequence composes the first 15 amino acid residues of the I-309 mimetic.23. The composition of claim 19, wherein the conserved amino acidsequence is selected from a group consisting of SEQ ID NO:974, variante3, and conservative amino acid substitutions thereof, and has thefollowing general structure: (SEQ ID NO:974)RNH-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala-Ile-Leu-Cys-Tyr-Arg-Asn-Thr-Ser-Ser-Ile- (OH)NH₂.


24. The composition of claim 19, wherein the I-309 mimetic is selectedfrom a group consisting of SEQ ID:1637 and conservative amino acidsubstitutions thereof, and has the following structure: (SEQ ID NO:1637)H₂N-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala-Ile-Leu-Cys-Tyr-Arg-Asn-Thr-Ser-Ser-Ile- NH₂.


25. The composition of claim 19, wherein the I-309 mimetic is selectedfrom a group consisting of SEQ ID NO:973, variant e2, and conservativeamino acid substitutions thereof, and has the following generalstructure: (SEQ ID NO:973)RNH-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala-Ile-Leu-(OH)NH₂.


26. The composition of claim 19, wherein the I-309 mimetic is selectedfrom a group consisting of SEQ ID NO:974, variant e3, and conservativeamino acid substitutions thereof, and has the following generalstructure: (SEQ ID NO:974)RNH-Ala-Phe-Ser-Phe-Ala-Glu-Gln-Glu-Ile-Pro-Leu-Arg-Ala-Ile-Leu-Cys-Tyr-Arg-Asn-Thr-Ser-Ser-Ile- (OH)NH₂.


27. An I-309 mimetic comprising an N-terminal region and a C-terminalregion, wherein the N-terminal region or C-terminal region comprises aconserved amino acid sequence selected from a group consisting of SEQ IDNO:975, variant e4, and conservative amino acid substitutions thereof,and has the following general structure: (SEQ ID NO:975)RNH-Ala-Tyr-Arg-Asn-Thr-Ser-Ser-Ile-Cys-Ser-Asn-Glu-Gly-Leu-Ile-Phe-Lys-Leu-Lys-Arg-Gly-Lys-Glu- Ala-(OH)NH₂;

wherein, R is an N-terminal modifier comprising a component selectedfrom a group consisting of a hydrogen, a poly(ethylene glycol) orderivative thereof, a diagnostic label, an acyl group, an acetyl group,and a modifier capable of reducing the ability of the I-309 mimetic toact as a substrate for aminopeptidases; and, the (OH)NH₂ is a hydroxy oramine group that comprises the C-terminal region, or attaches to anycombination of additional amino acid residues composing the C-terminalregion; and, the I-309 mimetic consists essentially of the conservedamino acid sequence and from 0 to 10 additional amino acid residues ofany combination.
 28. The composition of claim 27, wherein R comprises apoly(ethylene glycol), a glycosaminoglycan, or derivative thereof, eachhaving a molecular weight of less than about 20,000 Daltons.
 29. Amethod of increasing an I-309-mediated activity of a cell having anI-309 receptor comprising binding the I-309 receptor of the cell withthe I-309 mimetic of claim
 13. 30. A method of increasing anI-309-mediated activity of a cell having an I-309 receptor comprisingbinding the I-309 receptor of the cell with the I-309 mimetic of claim20.
 31. A method of increasing an I-309-mediated activity of a cellhaving an I-309 receptor comprising binding the I-309 receptor of thecell with the I-309 mimetic of claim 28.